Journal of Pharmaceutical Chemistry 2022-07-20T14:43:15+00:00 Venkatesan Jayaprakash, PhD Open Journal Systems <p>JPC is an open-access online peer-reviewed journal, publishing research articles from pharmaceutical sciences and its allied disciplines.</p> #113: Identification of newer hits as potential FAK inhibitors using in-silico methods 2022-01-07T17:22:12+00:00 Sahaya Nadar Tabassum Khan <p><span class="TextRun SCXW178787219 BCX0" lang="EN-IN" xml:lang="EN-IN" data-contrast="none"><span class="NormalTextRun SCXW178787219 BCX0">Focal adhesion kinase (FAK), a protein tyrosine kinase has been found to be overexpressed in cancer cells and plays a pivotal role in the proliferation of </span><span class="NormalTextRun SCXW178787219 BCX0">tumour</span><span class="NormalTextRun SCXW178787219 BCX0"> malignancy. By far, there is no FDA approved and marketed drug as FAK inhibitor for clinical use. This calls for a dire need to advance an area of active FAK inhibitors as potential anticancer entities. In the present study, applying appropriate filters in the ZINC database, 631 compounds were selected and virtually screened by using </span><span class="NormalTextRun SpellingErrorV2 SCXW178787219 BCX0">Autodock</span><span class="NormalTextRun SCXW178787219 BCX0"> Vina in </span><span class="NormalTextRun SpellingErrorV2 SCXW178787219 BCX0">PyRx</span><span class="NormalTextRun SCXW178787219 BCX0"> 0.8. Further the Lipinski’s Rule of five was applied on the best hits identified through molecular docking studies to find their druglikeness using </span><span class="NormalTextRun SpellingErrorV2 SCXW178787219 BCX0">SwissADME</span><span class="NormalTextRun SCXW178787219 BCX0">. The compounds were further screened for their toxicity by Pro Tox II. Our analysis resulted in identifying four hits, compounds ZINC95595125, ZINC43200601, ZINC40395224 and ZINC95593660 which exhibited good binding score along with passing the ADMET evaluations making these ligands a primary choice to be tested experimentally. The identified hits displayed good binding interaction with the FAK enzyme (PBD: 2ETM) and can be considered as potential leads. Further in-vitro and in-vivo anticancer activity against selected cell lines in which FAK are overexpressed can be carried out for these identified compounds.</span></span><span class="EOP SCXW178787219 BCX0" data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559685&quot;:296,&quot;335559737&quot;:15,&quot;335559739&quot;:5,&quot;335559740&quot;:238}"> </span></p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #1 NSAIDs’ antimicrobial mechanisms of action by inhibiting drug efflux and biofilm formation 2022-01-18T11:09:21+00:00 Sanjib Bhakta <p>The rise of antimicrobial drug resistance (AMR) in tuberculosis (TB) and non-tubercular mycobacte-<br>rial (NTM) infection coupled with the shortage of new antibiotics has elevated the global infectious<br>disease to a major global health priority. Our studies revealed that carprofen, a non-steroidal anti-<br>inflammatory drug (NSAID), inhibited the growth of replicating, non-replicating and multi-drug-<br>resistant clinical isolates of M. tuberculosis. We have approached to investigate the mechanism<br>through which NSAIDs eliminate the infection. Integrative molecular and microbiological inquiries<br>showed that carprofen, a bactericidal drug, inhibited bacterial drug-efflux mechanisms. Carprofen<br>also restricted mycobacterial biofilm-like growth, highlighting the requirement of efflux-mediated<br>communicative systems for the formation of biofilms. Transcriptome profiling revealed that carpro-<br>fen likely acts by targeting fundamental molecular machine through the disruption of membrane<br>potential, which may explain why spontaneous drug-resistant mutants could not be isolated in labo-<br>ratory practice due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomod-<br>ulatory drug has the potential to reverse TB antimicrobial drug resistance, offering a prospective path<br>to clinical trials of novel chemotherapeutic combinations.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #2 Extraction of Naturally Occuring Cannabinoids : Recent Advances 2022-01-18T11:22:42+00:00 Satyajit Sarker <p>Cannabinoids are the compounds that bind to cannabinoid receptors (endocannabinoid system), and they are one of the most investigated groups of natural products. <em>Cannabis sativa</em> L. (family:Cannabaceae), an herbaceous medicinal plant from Central Asia, produces most of the ca. 150 naturally occurring cannabinoids, which are commonly known as ‘phytocannabinoids’. Among them, Δ9 tetrahydrocannabinol (Δ9-THC or simply, THC) and cannabidiol (CBD) are the two major cannabinoids. Δ9-THC mainly contributes to the psychoactive property of <em>C. sativa</em>, whereas CBD displays anti-psychoactive property. A few other plants are also known to produce cannabinoids, for example, <em>Acmella oleraceae</em>, <em>Echinacea angustifolia</em>, <em>Echinacea purpurea</em>, <em>Helichrysum umbraculigerum</em> and<br><em>Radula marginate</em>. There are several methods available for the extraction of natural cannabinoids from various matrices, e.g., plant materials, medicinal and cosmetic products and human biological samples. In addition to classical maceration with organic solvents, several other methods like pressurized solvent extraction, solvent heat reflux, Soxhlet extraction, supercritical fluid extraction, ultrasound-assisted extraction and microwave-assisted extraction, are now routinely used nowadays for the extraction of cannabinoids. However, the choice of any extraction method, among other things, depends on the matrix where cannabinoids need to be extracted from, and contributes to the success of subsequent analytical methods for the analysis of cannabinoids. This talk will provide a critical overview of the literature published during the last decade on the use of various extraction methods for the extraction of naturally occurring cannabinoids from various matrices.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #3 Assessment of drug-drug interaction in pediatric drug development: Application of physiology-based pharmacokinetic modeling 2022-01-18T11:55:49+00:00 Jaydeep Sinha <p>Assessment of pharmacokinetic (PK) drug-drug interaction (DDI) is an important requirement of drug development. This is necessary because characterizing the clinically relevant DDIs inform the dose adjustment strategy in patients receiving polypharmacy. However, typical drug development trials are restricted to adult population only (i.e., excluding children) due to ethical and logistical constraints. This leaves the pediatric population as ‘therapeutically orphan’, because the safe and effective dosage for this population are not formally determined during typical drug development. As a result, drug dosing in the pediatric clinics are largely off-label, which impose significant risk to this special population. In addition to this, presence of DDIs further increase the risk. Unlike adults, dedicated DDI studies are rare in children, primarily because, most clinical pharmacology studies in pediatric patients are done opportunistically. Therefore, assessment of DDI in children becomes challenging using the conventional methods used in adults. Physiology-based pharmacokinetic (PBPK) modeling, in this context, is useful to address the gap. PBPK modeling has the unique ability to predict the PK of a drug by integrating the drug-specific properties with the physiological variables of the target population, obviating the need of extensive clinical data. Therefore, application of PBPK modeling is increasing in understanding the possible DDI implications in pediatric dose adjustment. This work demonstrates the use of PBPK modeling in understanding the DDI potential of enzyme-inducing antiepileptic drugs (EIAEDs) on the PK of oxcarbazepine and levetiracetam, two new generation antiepileptic drugs (AEDs), frequently used in pediatric epileptic patients.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #4 Computer-aided drug discovery: From small compounds to protein inhibitors against tyrosine kinase of EGFR for cancer therapy 2022-01-18T12:00:15+00:00 Kiattawee Choowongkomon <p>Computational studies are an essential part of research in Biochemistry today. The goal of the theoretical investigation of biochemical processes is to gain a deeper insight into the molecular mechanism behind the process of study. It can further be used to predict the results of experiments. Protein Bioinformatics is a useful technique to understand biochemical processes of proteins on various levels including protein modeling, protein docking, and protein molecular dynamics. In our group, we focus on the anticancer targeted protein, the epidermal growth factor receptor (EGFR). This protein plays a crucial role in cellular signaling pathways that regulates key functions, especially proliferation. EGFR abnormalities have been associated with several types of human cancer. Nowadays, there are cancer-treated drugs that inhibit the activity of the tyrosine kinase (TK) domain of EGFR – a signaling part of this protein. However, each drug specifically treats with each cancer type and some tumor patients have resisted to those drugs. The Discovery of better new efficient inhibitors is extremely needed. The virtual screening of medicinal plant compound databases against EGFR-TK has been used to discover new inhibitors. These compounds were tested on enzymatic inhibiting assay and non-small cell lung cancer cells, A549.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #5 Phytocompounds in drug discovery and development: Control of cancer and antibiotic resistance 2022-01-18T12:04:49+00:00 Velmurugan Devadasan <p>Herbal medicine is widely used globally to treat various diseases. Even though it does not lead to an immediate cure, the side effects are less compared to allopathic medicine. Cancer is one of the dreadful diseases killing millions of people worldwide. Antibiotic resistance is the major problem to tackle now as resistance had developed to many antibiotics. The Discovery of new antibiotics is very much delayed. In both problems, herbal medicine comes as a remedy. Literature shows that there are phytocompounds that can control/cure various types of cancer and also some of them act alone as antibacterials or act as adjuvants along with the resistant antibiotics in reversing the antibiotic resistance. The presentation will cover the research outcome related to the above two problems based on the work carried out in herbal medicine for the past 15 years. Details will be presented on the role of a phytocompound from a rhizome in treating colon cancer, breast cancer, and lung cancer. Some novel herbs will be discussed. To validate the above-said properties of the herbs, molecular docking had also been carried out for the related phytocompounds with relevant targets along with the drugs being used to treat the ailments.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #6 A new similarity-based read-across algorithm for the prediction of small datasets: Case studies with nano-toxicity data 2022-01-18T12:08:24+00:00 Kunal Roy <p>Nanotechnology is an important area of science developed in 21 st century, and it is being further advanced with time. Various new and modern technologies are utilized to produce different nanomaterials and nanoparticles nowadays, and these are used in various fields of industries and society. Due to their random use, the nanomaterials are dumped improperly affecting the environment adversely. They can pass the plasma membrane with ease due to their small particle size and hence can cause toxicity also. The regulatory agencies are working continuously to assess the risk associated with the nanoparticles and nanomaterials. They rely mostly on computational toxicity prediction to avoid the complexities associated with laboratory experimentation. QSAR and Read across are mostly used to fill the data gaps and for the risk and hazard assessment. In the present communication, we discuss a new similarity-based read-across algorithm for the prediction of toxicity (biological activity in general) of untested compounds from structural analogues. Three similarity estimation techniques such as, Euclidean distance based similarity, Gaussian kernel function similarity, and Laplacian kernel function similarity are used in this algorithm. The new algorithm is properly validated against three published nanotoxicity datasets. The quality of predictions depends on the selection of the distance threshold, similarity threshold, and the number of most similar training compounds. In this work, best predictions were obtained after selecting 0.4 – 0.5 as the distance threshold, 0.00 – 0.05 as the similarity threshold, and 2– 5 as the number of most similar training compounds. After toxicity prediction of test set compounds, the external validation metrics such as Q 2 ext_F1 , Q 2 ext_F2 , RMSEp were calculated. The computed metric values clearly justify the efficiency of the new read-across method and accuracy of the generated data by the proposed algorithm. A java based computer program (available at has also been developed based on the proposed algorithm which can effectively predict the toxicity of unknown NPs after providing the structural information of chemical analogues. The new algorithm and the program can be used for the data gap filling, prioritizing existing and new NPs, and for the risk assessments of NPs.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #7 Exploring the biosafety profile of novel biopoymeric nanoparti- cles in drug targeting 2022-01-18T12:12:54+00:00 Sushama Talegaonkar <p>Biomaterials can be considered safe, but at nano-size even a biomaterial can pose serious toxic issues to humans as well as a threat to the environment when compared to their macro or micro-sized counterparts. In humans, due to small size of nanocarriers, they can easily cross biological membrane and long exposure leads to their accumulation in cells, tissues and blood. Nanocarriers have unique surface chemistry and a huge surface area. Their highly reactive surface acts as a catalyst in the formation of reactive oxygen species (ROS), which in turn causes the generation of increased oxidative stress leading to lipid peroxidation, mitochondrial and DNA damage and ultimate cell death. Thus it is essential to establish the safety profile of a nanoformulation before it can be a part of the biomedical application. So, cytotoxicity and hemocompatibility of blank novel lignin nanoparticles were studied to ascertain the safety of lignin nanoparticles and the Drosophila melanogaster model was used to study the possible genotoxicity of blank nanoparticles causing behavioural and phenotypical alterations. After establishing the safety profile of optimized blank lignin nanoparticles (BLNPs), exhaustive blood compatibility studies on BLNPs, were carried out as these particles were designed for the intravenous administration.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #8 Nanotechnology in healthcare: Are we in the right direction? 2022-01-18T12:15:51+00:00 Vandana B Patravale <p>Nanotechnology is revolutionizing global industrial output and pharmaceutical industry is showing immense interest in nanoproducts owing to the emerging era of infectious diseases. The global nanotechnology healthcare market is expected to grow at a CAGR of around 11.9% in the period ranging from 2020 to 2026 and is estimated to reach USD 461, 252 million by 2026. The sole share of this segment will ensure a technological leap in the future of pharmaceutical R&amp;D sector. The ongoing pandemic has showed us the grave intensity of how vicious an infectious disease can get if arrived unannounced. The level of socio-economic impact that is being witnessed due to the Covid-19 pandemic is beyond imagination and forces us to think towards the development of versatile platforms that can help combat any such unknown disease in the future. This implies not only to the therapeutic platforms but also towards the diagnostic and prophylactic areas. Considering the importance and need of research in these areas, we at VBP Research Group have put our best foot forward and have developed technologies encompassing novel nanotechnology-based strategies pertaining to the diagnosis, prophylaxis as well as therapy of infectious diseases. The presentation will comprise a discussion of the case studies pertaining to the diagnosis of Brucellosis and further development of a green nanotechnology-based vaccine, both being award winning patented ideas. Our patented antimalarial platform based on nanostructured lipid carriers (NLCs) will be discussed in depth. The presentation will give an overview of the need for research in nanotechnology in the healthcare sector in today’s times and will pave way for a generation of many new ideas to take this research in the right direction.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #9 New herbal drug discovery for sickle cell disease: From ethnopharmacological claims to commercialization 2022-01-18T12:19:23+00:00 Vinod Rangari <p>Sickle cell disease is an inherited blood disorder that affects red blood cells. People with sickle cell disease have red blood cells that contain mostly hemoglobin S, an abnormal type of hemoglobin. The most common being Sickle Cell Anemia (SS), Sickle-Hemoglobin C Disease (SC), Sickle Beta-Plus Thalassemia and Sickle Beta-Zero Thalassemia. Health maintenance for patients with sickle cell disease starts with early diagnosis, preferably in the newborn period and includes penicillin prophylaxis, vaccination against Pneumococcus bacteria and folic acid supplementation. Patients frequently experience a vicious circle of events called a “Sickle cell disease crisis”, in which low oxygen tension in tissue causes sickling, which leads to ruptured RBC and further leads to a serious decrease in RBC count and more sickling which often causes death. In search for a substance that can prevent red blood cells from sickling without causing harm to other parts of the body, hydroxyurea was found to reduce the frequency of severe pain, acute chest syndrome and the need for blood transfusions in adult patients with sickle cell disease. The health care cost of the management of sickle cell disease patients is disproportionately high compared to the number of people afflicted by the disease. Poor people cannot afford the high cost of treatment. Due to the debilitating effect and cost of managing sickle cell disease, research has been ongoing to determine the efficacy of the use of medicinal plants to tackle the multiple challenges presented in sickle cell disease. It is therefore evident that there is a very high need of new drugs which must have low toxicity and marked antisickling activity. Literature survey revealed many plants having significant antisickling and some of them are used by medical practitioners in certain parts of the world for treating Sickle cell anemia. However, despite the long-standing problem of sickle cell disease, the above information did not lead to the development of a standardized remedy for the treatment and management of Sickle cell anemia. The Research work discussed herewith comprises the development of an effective pharmaceutical dosage composition of the Wrightia tinctoria family Apocyanaceae, seeds extract for the treatment and management of Sickle cell disease. The studies include acute and sub-acute toxicity studies, Antisickling assay, and the further clinical studies of the formulation. The success story of the new drug discovery using the traditional Indian medicinal plant and its ethnomedical history has been unraveled in detail.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #15 Biogenic silver nanoparticles of Jhad Beri: Synthesis, characterization and their antimicrobial screening 2022-01-18T12:23:29+00:00 Vikram Kumar <p>In the recent era of research and development, silver nanoparticles (AgNPs) are the most attractive nanomaterial in the development of nanomedicines due to their specific and distinctive physiochemical properties. Nanotechnology deals with the nanoparticles having a size of 1-100 nm in one dimension used significantly concerning medical chemistry, atomic physics, and all other known fields. These particles can be prepared easily by different physical, chemical, and biological approaches. During the formation of AgNPs, the reduction of Ag<sup>+++ </sup>to Agº occurs in presence of reducing and stabilizing agents which are naturally present in fungi, bacteria, yeast, and plants. In this study, we fabricate the AgNPs using the pineapple peels extract and characterization and optimization were carried out using the UV spectrophotometer, FTIR, and SEM techniques. Silver nanoparticles of <em>Ananas comosus</em> peel extract show the absorbance peak at around 410 nm analyzed by UV-Vis spectroscopy and their spherical shape and size (50 nm to 80 nm) was confirmed by the SEM analysis. FTIR analysis broke the point that the carbonyl group of reducing sugar stabilized the silver nanoparticles. These nanoparticles showed significant antimicrobial activity against <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>. In the future researcher can explore the biomedical properties for the preparation of biosensors using AgNPs and their application in medicine by using the herbal medium.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #16 Exploring the potential of curcumin and epigallocatechin in osteoarthritis by network pharmacological approach 2022-01-28T01:19:47+00:00 Srikant Garje Abhay Harsulkar <p class="p1">Osteoarthritis (OA) is a non-communicable disorder of multiple etiologies/origins, estimated to affect</p> <p class="p1">more than 500 million people worldwide which is 7% of the world population. while there are no</p> <p class="p1">pharmacological interventions other than pain management, understanding the mechanism and intertwined</p> <p class="p1">pathways is essential for developing a formulation addressing this multifactorial disorder.</p> <p class="p1">We employed a combination of software and database explorations to determine the antioxidant and</p> <p class="p1">anti-inflammatory properties of curcumin and green tea in this study. For data mining and network</p> <p class="p1">the data was enriched using String v11.5, KEGG, and Gene Ontology (GO) to comprehend OA cellular</p> <p class="p1">processes and phytoconstituent’s drug potential. The possible targets associated with bioactive</p> <p class="p1">components of curcumin and green tea were segregated and corresponding genes associated with humans</p> <p class="p1">were analyzed. The protein-protein interaction (PPI) associated with genes were analyzed and</p> <p class="p1">possible connections of OA-associated genes with critical signaling pathways, like the Hypoxia inducible</p> <p class="p1">factor-1 (HIF-1) signaling pathway, Apelin signaling pathway, arginine proline metabolism,</p> <p class="p1">and arachidonic pathway were discovered through network pharmacological studies. The network</p> <p class="p1">pharmacological study found the curcumin and green tea bioactive components such as Demethoxycurcumin</p> <p class="p1">and Epigallocatechin gallate targets the HIF-1 signaling pathway, Apelin signaling pathway,</p> <p class="p1">arginine proline pathway simultaneously. Imbalance in the HIF-1 Signaling pathway leads to</p> <p class="p1">OA development via destabilizing the balance of Reactive Oxygen Species (ROS) in Synoviocytes.</p> <p class="p1">Similarly, the arachidonic pathway is associated with nitric oxide formation and oxidative stress.</p> <p class="p1">Curcumin and Green tea have synergistic potential action when used towards OA. In addition, the</p> <p class="p1">bioactive components of these molecules will be tested as potential treatments for OA and related</p> <p class="p1">illnesses.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #19 Chemically modified xanthan gum as a potential carrier for a model drug Lornoxicam 2022-01-28T01:25:18+00:00 Sandip Murtale <p class="p1">This study investigated the utility of chemically modified xanthan gum (XG) for controlled drug delivery of Lornoxicam. Lornoxicam belongs to an oxicam class of nonsteroidal anti-inflammatory drugs. It inhibits the cyclooxygenase enzyme and thereby interferes with prostaglandins synthesis. Chemical modification of xanthan gum was carried out by using a thiol-esterification reaction employing thioglycolic acid (TGA) in the presence of a catalytic amount of hydrochloric acid. The reaction mixture was refluxed at 800 °C for 2.5 h. The above reaction mixture was cooled and precipitated by the addition of methanol. Microwave irradiated thiolated xanthan gum was also prepared by further irradiation of thiolated xanthan gum by microwave using 750 W frequency. The morphological characteristics, functional group, and thermal behavior of grafted gum were evaluated using SEM, FT-IR, XRD, and DSC. The controlled release applications of thiolated and microwave irradiated xanthan gum were comparatively evaluated with crude xanthan polymer by formulating tablets containing Lornoxicam as a model drug. Swelling and <em>in vitro</em> drug release behavior were also investigated. The results of FT-IR, DSC, and X-ray diffraction studies confirm that grafting was obtained. FT-IR study showed that in thiolated xanthan gum and microwave irradiated gum, additional peaks were observed, those which were not present previously in crude xanthan gum. The bands closer to 2568.00 cm<sup><span class="s1">−1 </span></sup> and 2584.70 cm<sup><span class="s1">−1 </span></sup> reflect the presence of SH stretch of the thiol group. Sustained-release tablets of Lornoxicam were prepared by direct compression technique using crude, thiolated, and microwave irradiated xanthan gum. The physical properties of compressed tablets like thickness, hardness, weight variation, and friability complied with the official limits. Free-flowing powder facilitates the formation of tablets with ideal properties. The swelling index of modified xanthan gum was high compared to native xanthan gum. <em>In vitro</em> release study conducted using phosphate buffer (pH 6.8) revealed a sustained release profile (24 h) of Lornoxicam from thiolated and irradiated xanthan gum as compared to crude xanthan. Thiolation and irradiated xanthan gum sustained the release of Lornoxicam over a prolonged period and could be a promising Lornoxicam carrier in oral delivery to enhance antinociceptive and anti-inflammatory efficiency.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #20 A Study on defensive effects of ferulic acid against neuronal inflammation persuaded by Cyclophosphamide 2022-01-28T01:33:05+00:00 Tejesvi Mishra Vinay Kumar <p class="p1">Neurotoxicity, which occurs due to progressive neuronal inflammation, is one of the globally leading challenges for clinical science nowadays. There are so many drugs that cause an inflammatory response to the nervous system as their adverse effects can result in critical complications to the patients. One such drug is Cyclophosphamide, a well-known anticancer and immunosuppressant drug. Cyclophosphamide and its metabolite (acrolein) have been proposed to be highly lipophilic moiety, cross the blood-brain barrier (BBB) and exhibit significant neurotoxicity. However, as of now, no adjuvant is available to mitigate this neurotoxic manifestation. Therefore, in the present study, ferulic acid (FRA) has been explored for possible neuroprotective effects against Cyclophosphamide-induced neurotoxicity in the Swiss Albino mice. Animals were divided into five groups (n=6) and treated with FRA for fourteen days and single-dose Cyclophosphamide was administered on the seventh day. Animals were subjected to neurobehavioral tests such as the Forced Swim Test (FST) and Morris Water Maze (MWM) test. On day fifteenth, animals were sacrificed and the brain was removed and used for biochemical analysis including parameters like antioxidant enzymes (SOD, CAT, GSH), lipid peroxidation, and pro-inflammatory cytokines. Treatment with FRA significantly reversed these behavioral and biochemical markers towards normal and mitigated Cyclophosphamide-induced neurotoxic manifestation. However, more detailed studies are needed to bring FRA from bench to bedside that it can be used as an adjuvant among chemotherapeutically treated patients.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #21 HPTLC standardization of Zandu haldi drops using curcumin as marker compound 2022-01-28T01:41:31+00:00 Aswatha Ram HN Keerthana Sanjay Kumar Putta Khoeli Tlhokomelo Joseph Aakarsh K <p>Zandu haldi drops is a one-of-a-kind recipe designed to improve immunity and overall health. It contains the goodness of saffron, cinnamon, cardamom, and black pepper, in addition to Haldi. Hence, the present work was aimed at the determination of haldi (turmeric) in Haldi drops by high-performance thin layer chromatography (HPTLC) with reference to the marker compound curcumin. The standard curve was prepared by weighing accurately 1 mg of curcumin in a volumetric flask, dissolved in methanol. Then make up the volume 10 mL with methanol to obtain a stock solution having 100 μg/mL concentration of curcumin. To prepare a working standard with a concentration of 10 g/mL, the standard stock solution of curcumin was diluted. The test sample solution of Zandu haldi drops was prepared by measuring 1 mL of the formulation in a 10 mL volumetric flask, dissolved in methanol. Then the volume was made up to 10 mL with diluent to obtain a stock solution having 100 µg/mL concentration. An accurately measured quantity is derived from this stock solution (1 mL) was dissolved in methanol in another 10 mL volumetric flask. Make up the volume to 10 mL with methanol to obtain a stock solution having 10 µg/mL concentration. The formulation extract and the marker compound were dissolved in methanol to make the concentration 10 µg/mL. The silica plates were preheated to remove the moisture and then the formulation extract and the standard samples were applied to it using the sample applicator. Then the samples were developed by the mobile phase [dichloromethane: methanol (99:1)]. After the development, the TLC plate was dried at room temperature. Then it was scanned in scanner3 at a wavelength of 421 nm. The amount of drug present was determined by comparing the sample’s peak area values to the standard’s, and the results were obtained. A curve of concentration Vs peak area of the standard was made and the concentration of curcumin present in the formulation solution used in this method was graphically extrapolated using the peak area of the formulation solution and was found to be 5.6 µg/mL. We conclude that the formulation Zandu haldi drops contains haldi as one of its ingredients and its presence was confirmed with reference to curcumin.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #22 Phytochemical investigation and in-vitro antioxidant activity of Memecylon umbellatum using DPPH method 2022-01-28T01:54:46+00:00 Chandrashekar KS Shilpee Chaudhary <p><em>Memecylon umellatum</em> Burm. (Synonym. <em>Memecylon edule</em>) belongs to the family Melastomataceae. It is a larges ornamental shrub or small tree found in the coastal region of deccan peninsula and eastern parts of India. The leaves of <em>Memecylon umbellatum</em> have been used traditionally to treat various infection and inflammatory conditions. The plant is the richest source of flavonoids and terpenoids which are known for anticancer activity. The present study was undertaken to isolate the phytoconstituents from ethyl acetate extract and to screen the antioxidant activity from the leaves of <em>Memecylon umbellatum</em>. Phytochemical investigation was carried out using column chromatographic technique and in-vitro antioxidant activity was evaluated using DPPH (1, 1-diphenyl-2-picryl hydrazyl) free radical scavenging assay. The chemical investigation of the leaves of <em>Memecylon umbellatum</em> led to the isolation of quercetin, pyrogallol, and gallic acid from ethyl acetate extract by successive extraction with different solvents and using column chromatography. These constituents were characterized by IR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and Mass spectral analysis. The ethyl acetate extract showed significant antioxidant activity. From the pharmacological studies carried out, it is evident that ethyl acetate extract of <em>Memecylon umbellatum</em> endowed significant antioxidant activity. The antioxidant activity may be due to quercetin, pyrogallol, and gallic acid. These constituents were isolated for the first time from this plant.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #25 Effect of Andrographis echioides on the larvae of dengue vector 2022-01-28T02:04:09+00:00 Prabhakaran S Sakthi Sundaram S Sengottuvelu S Sribharathi GS <p>Our main aim of the study was conducted to assess the larvicidal activity of <em>Andrographis echiodies</em> against the dengue vector <em>Aedes aegypti</em> larvae. 100 larvae of <em>Aedes aegypti</em> mosquitoes were exposed to each concentration of both ethanolic and methanolic crude extract of <em>Andrographis echiodies</em> in a volume of 100 mL. To minimize the error five replicates were employed with respective diluted alcoholic solutions as control. The percentage mortality of larvae at different concentrations of both alcoholic extracts and control were recorded after 24 h and 48 h of constant exposure followed by LC<sub>50</sub> and LC<sub>90</sub> determined. The effective and highest coefficient of determination (R<sup>2</sup>) was calculated using regression analysis. The result showed that LC<sub>50</sub> of methanolic extract of <em>Andrographis echiodies</em> at 24 h and 48 h was 290.02 and 224.22 ppm respectively. Similarly, LC<sub>90</sub> of methanolic extract of <em>Andrographis echioides</em> at 24 h and 48 h was 522.04 and 402.86 ppm respectively. The effective and highest coefficient of determination (R<sup>2</sup>) was 0.88 in 24 h of exposure. The ethanolic extract of <em>Andrographis echioides</em>, the LC<sub>50</sub> at 24 h and 48 h were 270.27 and 230.41 ppm respectively. Similarly, LC<sub>90</sub> of ethanolic extract of <em>Andrographis echiodies</em> at 24 h and 48 h was 485.96 and 414.75 ppm respectively. The effective and highest coefficient of determination (R<sup>2</sup>) was 0.94 in 24 h of exposure. Usage of synthetic chemical sources maybe results in resistance development and unsafe to nature. Drugs origin from nature, especially plants, and their secondary metabolite is considered eco-friendly, easily available, economical, and biologically safe. <em>Andrographis echiodies</em> exhibited larvicidal activity by enhancing the mortality of larvae while its exposure after 24 h and 48 h. Additionally, isolation of bioactive principles from <em>Andrographis echiodies</em> liable for its promising role in larvicidal potential and its structural elucidation may be necessitated to explore its mode of action.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #28 QbD based vesicular system development of Brassica nigra extract 2022-01-28T02:19:19+00:00 Surendra Agrawal Tapasya Yallatikar <p><em>Brassica nigra</em> is a traditional medicinal plant widely used in the treatment of asthma and rheumatism. The present study evaluated the antiarthritic properties of different doses of developed herbosome formulation and compared them with the plain extract. The herbosome formulation was developed using lipid concentration and cholesterol concentration as independent parameters wherein particle size and percentage entrapment efficiency were the dependent parameters. The developed formulation was evaluated for antiarthritic activity by adjuvant-induced arthritis. The optimized formulation revealed a mean particle size of 320 nm with 0.621 as PDI. The zeta potential values showed a mean of -36.2 mV revealing the stability of the formulation. Herbosomes with a dose of 400 mg/kg significantly decreased primary lesions and secondary lesions in adjuvant-induced arthritis. The findings of this experimental animal study indicate antiarthritic properties of <em>Brassica nigra</em> and thus provide pharmacological support to the traditional use of <em>Brassica nigra</em> in the treatment and management of painful, arthritic inflammatory conditions.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #29 Evaluation of antidiarrheal activity of ethanolic leaf extract of Phyllanthus amarus S. in wistar albino rats 2022-01-28T02:23:51+00:00 Sri Bharathi G S Crispus Omote Momanyi Lalitha V Sengottuvelu S Sivakumar T <p>Diarrhea is defined as the passage of more watery stools three or more times per day. It is the second leading cause of death in children under five years of old. Loperamide and other antibacterial drugs are usually preferred for treating diarrhea. Loperamide may cause addiction and cardiotoxicity. <em>Phyllanthus amarus S.</em> is traditionally used in treating many health problems such as jaundice, urinary bladder disturbances, wound healing, skin ulcer, etc. The aim of this study is to evaluate the antidiarrheal activity of ethanolic leaf extract of <em>Phyllanthus amarus S.</em> (EEPA). The preliminary phytochemical screening of <em>Phyllanthus amarus S.</em> was performed. The antidiarrheal activity is evaluated for EEPA with doses 250 mg/kg and 500 mg/kg. The models used to assess the antidiarrheal activity include charcoal meal test, castor-oil induced diarrhea, castor-oil enteropooling, and magnesium sulfate-induced diarrhea. The phytochemical screening confirmed the presence of saponins, tannins, triterpenoids, steroids, flavonoids, alkaloids, proteins, and carbohydrates in EEPA. In the charcoal meal test, the EEPA suppressed the propulsion of charcoal meals by reducing gastrointestinal motility (p&lt;0.01). In castor oil-induced diarrhea, the EEPA treated animals showed a significant decrease in water and feed intake and a decrease in the weight of fecal matter when compared to castor oil-treated rats (p&lt;0.01). In castor oil-induced enter polling in rats, the EEPA produced a decrease in the weight of the intestinal content by spasmolytic activity (p&lt;0.01). In magnesium sulfate-induced diarrhea, the EEPA treated groups showed a significant decrease in water and feed intake and a decrease in the weight of fecal matter (p&lt;0.01). The EEPA appeared to inhibit diarrhea by reducing the absorption of water from the intestine. This is due to the presence of tannins in it. Plants and plant derivatives have important advantages such as they are cheap with less or no side effects. The findings in the present study confirm the antidiarrheal activity of the ethanolic leaf extract of <em>Phyllanthus amarus S.</em> thus providing the scientific basis for the traditional use of this plant in the treatment of diarrhea and its effects.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #30 Evaluation of sunscreen activity of herbal cream 2022-01-28T02:31:57+00:00 Nagja Tripathi Riya Chitral <p>Excessive exposure to UV rays causes hyperpigmentation, premature aging, and skin cancer. Due to these harmful effects of UV radiation, there is a need to develop sunscreen formulations to heal and prevent sunburn and increase the level of protection from the UV rays. Flavonoids and phenolic compounds have a good capacity to absorb UV rays in UV-A region and possess good antioxidant activity. Aim of the study conducted was to develop herbal formulation for photoprotective activity. Liquorice root and pomegranate peel were selected for the study because they contain phenolics and flavonoids in abundance. Both methanolic extract and hydroalcoholic extract of individual herbal drugs were prepared. Total phenolic content of all extracts was determined by the Folin Ciocalteau method. The total flavonoid content of all extracts was measured by AlCl<sub>3 </sub>method. The antioxidant activity of all extracts was evaluated by DPPH assay method. The SPF (Sun Protection Factor) value of combined methanolic extract and combined ethanolic extract of both herbal drugs were determined by Mansur equation. Four cream formulations were prepared using different percentages of combined methanolic extracts and SPF value was evaluated. The physical parameters like appearance, spreadability, pH, and viscosity of all four cream formulations were also evaluated. Total phenolic content was found higher in the hydroalcoholic extract of pomegranate peel and total flavonoid content was found higher in methanolic extract of liquorice. IC<sub>50</sub> value of pomegranate peel methanolic extract was 64.5 µg/mL, and it showed good anti-oxidant potential. IC<sub>50</sub> value of liquorice hydroalcoholic extract was 53.7 µg/mL, so hydroalcoholic extract showed good antioxidant potential. Methanolic extract of both herbal drugs showed good photoprotective activity as compared to combined hydroalcoholic extract so methanolic extracts were selected for incorporation in the herbal cream formulation. It was observed that by increasing the concentration of extract from 2% to 8%, the SPF value of cream formulation increased. The herbal cream formulation containing 8% of combined methanolic extract of both liquorice root and pomegranate peel showed good physical characteristics and optimum photoprotective activity. So it can be concluded that liquorice root and pomegranate peel have good potential as sunscreen agents and they can be explored further to develop a safe and effective herbal cosmetic product for photoprotective activity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #33 Formulation and evaluation of Dexketoprofen proniosomal gel 2022-01-28T03:36:40+00:00 Tanu Bhargava Kamlesh Dashora <p>Current research is based on the development and differentiation of transdermal proniosome-based gel. The modified proniosomal gel shows good stability, release, following zero-order kinetics, maximum zeta power is ±49 mV. The pH of the whole composition was close to the skin pH 7.11 to 7.20 the drug content in the formulation was within an estimated range of 92-97%. The composition of the gel can be sorted as follows with regard to the viscosity of the drug: Dt3 &gt; Dt2 &gt; Dt9 &gt; Dt7 &gt; Dt4 &gt; Market gel &gt; Dt6 &gt; Dt5 &gt; Dt1 &gt; Dt8. Span 40 &amp; span 60 (50:50) proniosomal gel showed a drug release up to 12 h. The encapsulation efficiency of proniosomal gel formation ranges from 82.10% to 94.12%. Analysis of the proniosome-based niosome particle size shows that the SD (nm) particle size is 209.5 nm with a polydispersity index of 0.182.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #35 An overview of developing trends in apple cider vinegar research: A bibliometric analysis 2022-01-28T03:42:06+00:00 Smriti Tripathi <p>Apple cider vinegar (ACV) is one of the most widely used condiments for various pharmacological activities. The area of ACV research is a multi-dimensional and interdisciplinary research domain. The recent research works showed that ACV is not only beneficial for weight loss, antibacterial, antifungal, cardiovascular activity but also it has anti-cancer, anti-Alzheimer’s activity. Although there are numerous studies that have shown the beneficial activities of ACV, yet there is a dearth of key mechanism exploratory studies for these ACV activities. Thus, researchers must keep well-informed of associated developments to ensure an appropriate knowledge of the areas which required attention. In this study, a bibliometric analysis method was used to map the ACV research. Bibliometric analysis is a standard and demanding technique for exploring and analyzing huge volumes of scientific data. We aimed to perform a bibliometric analysis for the apple cider vinegar in the area of human health. The data was retrieved from the Scopus database, where a total of 327 publications related to ACV were identified. The 327 publications, published between 1975 to 2021, covered 295 Research articles, 13 review articles, 310 journals, 59 countries or territories. After the careful manual screening of the results, finally, 234 articles were selected to proceed for analysis. This data was analyzed using bibliometric software Vosviwer. This review study will help researchers to familiarize themselves with the research development of the apple cider vinegar domain so far, as well as with the areas required focus for future research.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #36 Development and validation of analytical method for simultaneous estimation of Telmisartan and Gallic acid by RP-HPLC 2022-01-28T03:46:02+00:00 Swadesh Kumar Pattanik Kishanta Kumar Pradhan <p>A simple, sensitive, rapid, reliable, and economic RP-HPLC method was developed &amp; validated for simultaneous estimation of Telmisartan and gallic acid in bulk and a pharmaceutical dosage form. One of the prominent causes of hypertension is oxidative stress produced by reactive oxygen species. Gallic acid is a polyphenolic drug, having a very good antioxidative property that reduces oxidative stress. Telmisartan is a well-known AT1 receptor blocker and comparatively safer among all antihypertensive drugs. Combined administration of both drugs will produce a synergistic effect against hypertension. This study gives an opportunity for standardization of combined formulation. Telmisartan and gallic acid were chromatographed by RP-HPLC Waters-1525 binary pump, C-18 Column (length- 250 mm, internal diameter- 4 mm, particle size- 5 µm) with mobile phase: methanol: water (60:40, pH – 3.5 adjusted by acetic acid). Sample prepared with the mobile phase. Flow rate: 1 mL/min., run Time: 12 min., injection volume: 20 µL, detection, and quantification were performed by using a deuterium lamp operated by BREEZE software. a very good resolution was observed at λ = 273 nm for both of the drugs. Calibration plots were established showing the dependence of response on the amount chromatographed. The linear regression analysis data for the calibration plots showed good linear relation with R<sup>2</sup>= 0.998 for peak area of both the drugs between concentration range of 5 50 µg/mL. For gallic acid Rt - 2.757 min, LOD- 1.045 µg/mL, LOQ- 3.167 µg/mL and for Telmisartan Rt - 7.910 min, LOD- 1.004 µg/mL, LOQ- 3.044 µg/mL respectively. The method was validated as per ICH guidelines &amp; can be adopted to validate and standardize other related pharmaceutical products.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #37 Design, synthesis and evaluation of the cholinesterase inhibitory potential of 5-chlorobenzimidazole derivatives for Alzheimer’s 2022-01-28T03:54:15+00:00 Sonal Pathak Archana Gurjar Christine Shing Wei Law Keng Yoon Yeong Suchita Vishwakarma <p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to a decline in cognitive function and behavior. It is characterized by depletion in acetylcholine and butyrylcholine, presence of amyloid deposits, formation of neurofibrillary tangles in the brain. Donepezil, an acetylcholinesterase inhibitor remains the leading compound for symptomatic relief of AD patients. Thus, cholinesterase is a promising target to explore the therapeutic effect for AD. By blocking AChE peripheral anionic site, its co-localization with amyloid fibrils can be restricted and hence limiting plaques deposition in different regions of the brain. Extending study towards the development of cholinesterase inhibitors may eventually prevent precipitation of amyloid plaques and neurofibrillary tangles hence justifying its targeted interest. Nitrogen-containing heterocyclic scaffolds are known to possess potential activity towards AD targets. Hence, we intend to explore the therapeutic effect of substituted 5 chlorobenzimidazole derivatives as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors with their neuroprotective role. Ligands were sketched and minimized with LigPrep under the force field of OPLS-2005 (Schrödinger’s Maestro release 2018-1). QikProp v.5.5 (Schrödinger’s Maestro release 2018-1) was accessed for in-silco ADME. 5-chlorobenzimidazole derivatives were synthesized with benign synthetic methods. The purified derivatives were characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance (<sup>1</sup>H-NMR). The masses of the target compounds were confirmed through LC-MS (ESI). In-vitro LPO (lipid peroxidation) assay was performed on rat brain. Cholinesterase inhibition was carried out on the synthesized derivatives using Ellman’s method. All the derivatives exhibited favourable drug like properties and the results were complying with the QikProp recommended range. In-vitro LPO assay results were in the range from 2.80 – 31.68 μM depicting their neuroprotective potential with Bz–6 being the most effective. In-vitro cholinesterase inhibition assay indicated that BZ series potentially inhibited BuChE over AChE. Substituted Bz-10 with IC<sub>50 </sub>4.25 mM was the most potent BuChE inhibitor. 5-chlorobenzimidazole derivatives showed favourable ADME parameters, portraying neuroprotection and cholinesterase inhibition. Cholinesterase inhibition was found to be more promising against BuChE as compared to AChE at 10 µM. Hence, these can act as effective candidates for symptomatic treatment of AD.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #38 Sub-acute toxicity profiling of Sansevieria cylindrica and Plumeria obtusa plant extracts in wistar albino rats 2022-01-28T04:25:49+00:00 Sunil Shewale Vrushali Bhalchim Maruti Shelar Shubham Padole Shital Satone Shweta Lembhe Sameer Parekh Pramod Pujari Vaishali Undale <p><em>Sansevieria cylindrica</em> (SC) and <em>Plumeria obtusa</em> (PO) plants have been investigated for diverse pharmacological activities, but the safety and/or mechanism of toxicity is still lacking in the literature. Subacute toxicity studies will add value to the drug's pharmacological profile. The dose of drugs for this study was decided by limit test. The present study evaluated the toxic potential of plant extract through repeat administration for 28 days in male and female wistar rats. An acute toxicity study was conducted initially and a limit dose was determined. Based on this data, sub-acute toxicity was planned and carried out with the oral administration of repeated doses of 200 mg/kg/day and 400 mg/kg/day; body weight (b.wt.) for 28 days. All animals were equally divided into three groups (n= 6) with each group containing 3 male and 3 female rats. The toxic signs, mortality, and body weight changes along with neurotoxicological assessments (Functional Observation Battery and Locomotor Activities) were recorded. On day1 and 29 the rats were anesthetized to collect blood for estimation of hematological and biochemical parameters. Animals were sacrificed to collect internal body organs for weighing and histopathological studies on day 29. The plant's extract has no major adverse effect on the body weight, food intake, biochemical and hematological parameters, and internal body organs. No mortality or any major sign of morbidity was recorded. However, minor variations were observed in treatment groups compared to the control group. Oral administration of SC and PO hydro-alcoholic extracts did not cause any systemic toxic effects. In conclusion, the no-observed-adverse-effect level (NOAEL) of these extracts in rats was found over a limited period after repeated administration and supports its exploration as a future medicine.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #39 Design, synthesis and studies of novel imidazoles 2022-01-28T04:40:43+00:00 Priyanka Chandra Swastika Ganguly Manik Ghosh <p>With reference to our previously reported work on imidazoles, herein our objectives are to report the molecular docking studies of the synthesized imidazole analogs 2(a-f) into the non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1-reverse transcriptase (PDB ID: 1RT2). The methodology consisted of the drawing of the chemical structures in Chem Office version and the docking of these compounds in the NNIBP of HIV-1- RT with the help of Autodock Vina software. Binding mode analysis of all the docked compounds was carried out in the non-nucleoside inhibitory binding pocket of HIV-1-reverse transcriptase (PDB ID: 1RT2). All the compounds except compound 2c showed different interactions with the NNIBP. H-bonding interactions were observed for compounds 2b, 2d, 2e &amp; 2f, whereas pi-pi-interactions were obtained for compounds 2a &amp; 2f. Predictive ADMET studies were carried out for all the compounds. All the compounds were found to have drug-like properties. Among all the compounds, compound 2a was found to have the highest dock score when compared to the standard Nevirapine, whereas the best interaction was obtained for compound 2f. It is hoped that compounds 2a {(E)-2-(2-methyl-4 nitro-1H-imidazol-1-yl)-3-phenyl-1-(p-tolyl)prop-2en-1-one} &amp; 2f {(E)-3-(3,4-dimethoxyphenyl)-2-(2-methyl-4-nitro-1H-imidazol-1 yl)-1-(p-tolyl)prop-2-en-1-one)} may act as a moiety which could be explored further for the synthesis of newer analogs which could act as non-nucleoside reverse transcriptase inhibitors against HIV-1- RT.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #40 Design, synthesis, and anti-inflammatory evaluation of coumarin pyrazoline hybrid with sulphonamide moieties: An in-silico approach 2022-01-28T04:45:17+00:00 Arulraj R Prabha T Sivakumar T Haritha P Manickavalli E Ramya L <p>The increasing cancer burden together with population growth as well as the changing prevalence of certain causes of cancer linked to social and economic development, the presence of drug resistance, etc. leads to the search for newer therapeutic agents. The aim of the present study is to synthesize the series of coumarin pyrazoline hybrid with sulphonamide derivatives for evaluating their in-vitro and in-vivo anti-inflammatory activity followed by in-silico docking study to evaluate their anticancer potency against the enzyme protein thyrosine kinase. The series of coumarin pyrazoline hybrid with sulphonamide derivatives were synthesized and characterized via IR, NMR, and MASS spectroscopy. The synthesized compounds were subjected to both in-vitro and in-vivo anti-inflammatory activity at a different dose of 150, 250, 350 mg/kg. Further to confirm their anticancer potency theoretically, an in-silico docking analysis was carried out to explore the potency against the enzyme protein thyrosine kinase (PDB ID: 1KE9). The in-vitro anti-inflammatory study results revealed that the coumarin pyrazoline analogues viz. compound CS1, CS2, and CS5 showed the noteworthy inhibition with the range of 78.53±1.19, 73.91±1.56, and 74.65±1.88, respectively when compared to the standard drug, Indomethacin, which showed 82.35±0.89 at 100 µg/mL. Whereas, the in-vivo acute model study showed viz. CS1, CS2, CS5, and CS6 gradually decreased in paw thickness at the hourly basis with the range of 0.45±0.19, 0.39±0.17, 0.42±0.18, and 0.35±0.51 mm, respectively for 50 mg/kg at 4<sup>th</sup> h when compared to standard, 0.31±0.17 mm. Similarly, the chronic model result showed the compounds viz. CS1, CS2, and CS5 possess the significant nearby decrease in weight of the cotton pellet as 68.57±4.56, 58.75±3.91, and 60.32±2.97, mg/kg, respectively while the standard drug showed 54.65 ± 3.65 mg/kg. In addition to this, the docking study reveals that coumarin pyrazoline analogues under observation viz. CS1-CS6, had a binding affinity between the range of -20.2747 to -26.2652 kcal/mol with enzyme protein thyrosine kinase (PDB ID: 1KE9), whereas, the standard co-crystal ligand showed the binding affinity of -19.3335 kcal/mol. Hence, the synthesized coumarin pyrazoline analogues showed a promising anti-inflammatory activity both in-vitro and in-vivo. These inflammatory response become chronic, lead to cell mutation and proliferation can result in the development of cancerous cells and thus, in near future, the synthesized compounds are further evaluated for their effect on anticancer activity. Besides, our in-silico study result strongly supports this hypothesis and these compounds might be a potential candidate for treating cancers. However, the detailed mechanism and further evaluation of their anticancer activity are under process.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #41 Effect of Boswellia serrata in 3-NP induced experimental huntington disease 2022-01-28T09:33:34+00:00 Chanchal Sharma Tejesvi Mishra <p>Huntington’s disease (HD), commonly known as Huntington’s chorea, is a hereditary neurodegenerative illness. Huntington’s disease is an autosomal dominant neurodegenerative condition marked by uncontrollable movements, cognitive impairment, and severe degradation of basal ganglia neurons in the neostriatum. Huntington’s disease (HD) causes cognitive and psychological disability due to neuronal degeneration in the brain. Several investigations have found that oxidative stress is the primary pathogenic component in HD. The current study seeks to assess the potential neuroprotective benefits of <em>Boswellia serrata</em> at three distinct oral dosages of 45 mg/kg, 90 mg/kg, and 180 mg/kg on 3-nitropropionic acid (3-NP)-induced HD. 3-nitropropionic acid (3-NP) is a toxin that inhibits the mitochondrial enzyme succinate dehydrogenase in the brain irreversibly. The 3-NP model is reliable for researching HD because it simulates a downstream pathway of cell death identified in the HD brain, especially mitochondrial dysfunction. In the current investigation, we used 3-NP at 10 mg/kg i.p. to induce HD in a rat model. This study looks at how effectively <em>Boswellia serrata</em> protects against HD. <em>Boswellia species</em> (<em>Burseraceae</em>) are widely utilized in herbal medicine across the world. Boswellia species, such as <em>Boswellia serrata</em>, produce oleo gum resin. Oleo gum resin can also be used to treat dysmenorrhea, gingivitis, wounds, ulcers, and as an anti-inflammatory agent. We will use 56 Wistar rats (8 per group) to assess biochemical and behavioral parameters. To our knowledge, this is the first study to look into the neuroprotective benefits of <em>Boswellia serrata</em> on 3-NP-induced HD.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #42 Ligand-based drug design for search of imidazole analogues as anti-Alzheimer agents 2022-01-28T09:37:24+00:00 Sonal Parmar Kalyani Memane Archana Gurjar <p>Alzheimer’s disease (AD) is a neurodegenerative disorder. Currently, more than 50 million people are suffering from dementia worldwide. Neuropathologically it is characterized by the presence of extracellular Amyloid β (Aβ) plaques and intracellular neurofibrillary Tau protein tangles in the brain. Literature reveals that a crucial target to relieve symptoms of AD is Acetylcholinesterase (AChE). Many heterocyclic compounds have been developed in past years as AChE inhibitors. The marketed ones are Donepezil, Rivastigmine, and Galantamine, all are nitrogen-containing drugs that have potential activity towards AChE. We have focused on a series of imidazole as AChE inhibitors. This scaffold was chosen due to its similarity with previously reported benzimidazole derivatives as AChE inhibitors. Computer-aided drug discovery broadly encompasses structure-based and ligand-based models. Ligand-based drug design (LBDD) methods mainly include pharmacophore modeling and QSAR (quantitative structure-activity relationship). These methods use ligand information for predicting the biological activity of test series, based on similarity/dissimilarity with structural features of previously known active ligands. Ligands were sketched and minimized with LigPrep3 (Schrodinger). In-silico ADME (Absorption, Distribution, Metabolism, Excretion) studies were accomplished using the QikProp V5.5 module (Schrodinger). Pharmacophore modeling was done using Phase V5.4 (Schrodinger). The atom-based 3D-QSAR software of Schrodinger’s Maestro release 2018-1.10 was used for QSAR studies. Various sets of molecules with a wide range of AChE inhibitory activity were chosen from the literature to get a robust model for hypotheses generation. Created hypotheses were three to five points model. The entire series of minimized analogues were screened upon the shortlisted hypotheses to align them and carried further for QSAR studies. Analogues showcasing favorable pharmacokinetic properties and good predicted activity from LBDD were subjected to synthesis. Characterization was performed by IR and NMR spectrometric techniques. Results of the in silico ADME studies predicted that all the analogues showcase drug likeness. LBDD study revealed that IM-1, IM-2, IM-7, and IM-18 exhibited nearly the same predicted activity as Donepezil, hence they may show good inhibitory AChE activity. Analogues that depict good activity can be subjected to in vitro pharmacological evaluations such as lipid peroxidation assay to assess the neuroprotective role, cholinesterase inhibition, and memory model study.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #43 Preliminary wound healing potential of Clarias batrachus collagen on excision wound model in wistar rats 2022-01-28T13:20:36+00:00 Pavithra J Sengottuvelu S Shila G Sri Bharathi G S <p>Wound healing is the progression of repair that follows injury to the skin and other soft tissues. Collagen, a chief structural protein has been discussed by many researchers for its active role in the natural healing process. Fish mainly contains type-I collagen and it contributes to the formation of the dermis layer of the skin. Based on the beneficial effects of collagen on wound healing, the study was conducted to evaluate the preliminary wound healing activity of <em>Clarias batrachus</em> skin on excision wound models in wistar albino rats. Collagen was extracted from the fish <em>Clarias batrachus</em> skin and processed to Acid Soluble collagen which was used to study the wound healing property against excision wound model in wistar rats. A full-thickness excision wound with a circular area of 1.5 cm was created. Two dose levels of 5% and 10% <em>Clarias batrachus</em> skin collagen were employed in the study. Povidone–Iodine ointment was used as a reference control. The parameters such as wound area and percentage wound contraction were measured at the end of the study. The test drug 5% of <em>Clarias batrachus</em> skin collagen on the 4<sup>th</sup> day showed a less significant (P&lt;0.05) decrease in the wound area and on 7<sup>th</sup> and 14<sup>th</sup> day showed more significant (P&lt;0.001) decrease in wound compared to vehicle control and maximum percentage of wound contraction of about 97.91% was observed on the 14<sup>th</sup> day. The test drug 10% of <em>Clarias batrachus</em> skin collagen showed a significant (P&lt;0.001) decrease in wound area on the 4<sup>th</sup>, 7<sup>th</sup>, and 14<sup>th</sup> day and a maximum percentage of wound contraction of about 99.31% was observed on the 14<sup>th</sup> day which was more than that of reference control Povidone–Iodine ointment. The conventional method involves the application of antibacterial agents and antibiotics which only prevent the wound from invading microorganisms. So our aim was to find a better way to increase the wound healing rate by directly administering collagen in the wound which is the important extracellular matrix involved in tissue regeneration. <em>Clarias batrachus</em> skin collagen extract gel (5%) and (10%) on the topical application in the excision wound model, increased the wound healing activity significantly. Therefore this study revealed that <em>Clarias batrachus</em>&nbsp;collagen has remarkable wound healing activity which is due to its direct contribution to extracellular matric.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #44 Evaluation of in-vitro and in-vivo anti-asthmatic activity of curcumin and vasicine 2022-01-28T13:30:18+00:00 Shila G Sengottuvelu S Haja Sherief S Lalitha V <p>Asthma is a condition in which a person’s airways become inflamed, narrow, and swell and produce extra mucus, which makes it difficult to breathe. Asthma can be minor or in some cases, it may lead to a life-threatening attack. Curcumin (<em>Curcuma longa</em>) and Vasicine (<em>Adathoda vasica</em>) are traditional Indian medicine used in the treatment of bronchial asthma. They have various pharmacological activities such as anti-inflammatory, bronchodilator and antioxidant. The aim of this study is to evaluate the in-vitro and in-vivo activity of curcumin and vasicine against airway inflammation. In in-vitro histamine-induced contraction on isolated guinea pig tracheal chain preparation method, the guinea pig tracheal chain is prepared and initial responses were recorded with histamine. After giving wash, responses were recorded in presence of a single constituent (curcumin 100 µg/mL and vasicine 30 µg/mL) and combination. In in-vivo ovalbumin (OVA) induced allergic airway inflammation mouse model, the animals were sensitized and challenged by Ovalbumin/ AloH. The BALB/c mice were administrated orally with curcumin(100 mg/kg) and vasicine (3mg/kg) alone and in combination, total and differential count in BALF and IgE level in serum was counted using ELISA. Contraction produced by histamine was antagonized and produced relaxation by the combination of curcumin and vasicine than single constituent. Treatment of mice with the curcumin and vasicine combination reduces the total and differential count of bronchoalveolar lavage fluid (BALF)(p&lt;0.001) and IgE serum level in the mice(p&lt;0.001) when compared with curcumin and vasicine alone treated groups(p&lt;0.01). The data indicate that the combination of drugs produces relaxation of smooth muscle, reduced the total and differential count and IgE, level in serum. Therefore this study revealed that curcumin and vasicine combination shows a synergetic effect on the inhibition of inflammatory mediators which is useful to treat asthma. From the result, it was concluded that curcumin and vasicine may be an alternative for the conventional drug against asthma.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #45 Evaluation of anthelmintic activity of hydroalcoholic extracts of Acalypha indica leaves and its phytochemical analysis using Fourier Transform Infrared 2022-01-28T13:38:03+00:00 John Staines M Gladys Kalpana K Rajesh Kumar E Maheswaran P <p>Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. <em>Acalypha indica</em> is a medicinal plant that is widely used in traditional medicine to treat many diseases like insect bites, infections, sore throat, ulcers, etc. The aim of this study is to evaluate the anthelmintic activity of hydroalcoholic extracts of <em>Acalypha indica</em> leaves and its phytochemical analysis using Fourier transform infrared. Phytochemical constituents of hydroalcoholic extracts of <em>Acalypha indica</em> leaves were analyzed using Fourier transform infrared (FTIR). 50 mL of a formulation containing different concentrations of crude aqueous extract (10, 25, 50, and 100 mg/mL in distilled water) were prepared and 6 worms of the same type were placed in it and the anthelmintic activity of hydroalcoholic extracts of <em>Acalypha indica</em> leaves against earthworm Pheretima posthuma was evaluated. As a result of FTIR analysis, the hydroalcoholic extracts of <em>Acalypha indica</em> leaves showed the presence of coumarin, flavonoids, tannin, phenolic compound, saponin, quinone, and alkaloids. In investigating the anthelmintic action of formulation against adult Indian earthworms, the values of paralytic time and death time of formulation were less when compared to the positive control Albendazole. The ethanolic extract at dose 40 mg/mL caused paralysis in 12 min and death in 110 min against <em>Pheretima posthuma</em> compared to the reference standard Albendazole (10 mg/mL) showed the same at paralysis time 28 min and death time 130 min. The ethanolic extract of <em>Acalypha indica</em> leaves exhibits anthelmintic activity in dose-dependent manner. The ethanolic extract showed significant anthelmintic activity when compared to the reference drug Albendazole. The present work concludes that the hydroalcoholic extracts of <em>Acalypha indica</em> leaves can act as a more suitable herbal treatment against helminths infection and further effectively formulate as an effective dosage form.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #46 Assessment of androgen receptor binding affinity of endocrine disruptors: A 2D-QSAR approach 2022-01-28T13:46:26+00:00 Arkaprava Banerjee Priyanka De Kunal Roy <p>Endocrine disruptor compounds (EDCs) are synthetic or natural molecules in the environment that promote adverse modifications of endogenous hormone regulation in humans and/or in animals. By interfering with the body’s endocrine system, these chemicals produce adverse developmental, reproductive, neurological, and immune effects in animals, abnormal growth patterns, and neurodevelopmental delays in children. Among these, certain compounds mimic the role of androgen which is responsible for controlling the development and maintenance of male sexual characteristics. In the present research, we have utilized the application of a two-dimensional quantitative structure-activity relationship (2D-QSAR) modeling technique to analyze the structural features of these chemicals responsible for binding to the androgen receptors (logRBA) in rats. We have collected the androgen receptor binding data from the EDKB database ( We have then employed the DTC-QSAR tool, available at for dataset division, feature selection, and model development. This tool is a complete package providing a user-friendly, easy-to-use GUI to develop regression or classification-based QSAR models involving variable selection techniques such as genetic algorithm and best subset selection. Dataset division was done by the euclidean distance approach method followed by feature selection using the genetic algorithm (GA) technique. The best descriptor combination selection for the pooled descriptors from the best GA-derived models was done using the tool Best Subset Selection v2.1 available at The final partial least squares (PLS) model was evaluated using various stringent validation criteria. The developed model is robust, predictive, and should be a useful tool to predict the binding nature of EDCs to the androgen receptor. From the model, we interpreted that hydrophobicity in terms of octanol-water partition coefficient, aliphatic -CH group count, the bulkiness of the structure, in addition to a number of non-aromatic conjugated carbon atoms (sp2 hybridized), presence of CF<sub>3</sub> group, percentage of nitrogen present in the compounds contribute to the receptor binding affinity and thus increase toxicity, while the presence of electron-rich features like aromaticity in a molecule and presence of polar groups like alcohol, phenol or carboxyl groups decrease the receptor binding affinity and reduce toxicity. Additionally, we have also performed chemical read-across using Read-Across-v2.0 available from, and the results for the external validation metrics were found to be better in the euclidean distance-based similarity considerations.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #47 Formulation development and evaluation of oral care herbal product from Azadiracta indicia 2022-01-28T14:04:48+00:00 Jana A V Dhasaratha Sharma L K Kishor Kumar V Nikhil P S <p><em>Azadiracta indicia</em> is an herbal medicine which is used for various ailments. We have made efforts to bring a new formulation of toothpaste with more stable in terms of rheological behavior, long-term protection and stability in diverse conditions. The aim of the present study is the formulation of new herbal toothpaste and its evaluations along with stability studies. The plant <em>Azadiracta indicia</em> (Neem) is used for the preparation. Plant leaves and stems are separately extracted and used for the formulation. The four different formulations of three different concentrations of 0.25%, 0.50%, 0.75% were coded as <em>Azadiracta indicia</em> leaf extract (AILE), <em>Azadiracta indicia</em> stem extract (AISE), leaf paste (LP) &amp; stem paste (SP) and are evaluated for the studies. The evaluation parameters are hard and sharp edges abrasive particles, spread ability in cm, pH, foaming power in mL and the stability tests of antimicrobial activity such as antibacterial &amp; antifungal activities are done by cup plate method using Ciprofloxacin and Amphotericin B as standard drugs by taking the tests of different concentrations 250 µg, 500 µg, 750 µg, &amp; 1000 µg are incubated at 280 °C for 24 h, the zone of inhibition is measured in mm by using bacterias (<em>Klebsiella pneumonia</em>, <em>Escherichia coli</em>, <em>Staphylococcus aurous</em>, <em>Pseudomonas aeruginosa</em>) and fungi (<em>Candida albicans</em>). The hard and sharp edges abrasive particles are absent in every formulation, spread ability is maximum in AILE (0.25%) than LP (0.25%), foam formation will increase with the increase in concentration in the case of extracts and decreases with increase in concentration in the case of powder formulations, pH is maximum for LP formulation in higher concentration (0.75%) and minimum for AILE at a lower concentration (0.25%) only. The stability studies of toothpaste is having a good zone of inhibition with comparing the standard drugs. The developed toothpaste could be utilized in the treatment of various periodontal diseases. Further pharmacological evaluations, toxicological studies, and possible isolation of the therapeutic antibacterial from this plant are future challenges.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #48 A novel UPLC method development, validation and forced degradation studies on Lamivudine and Dolutegravir in combined pharmaceutical dosage form 2022-01-28T14:13:26+00:00 Kamalakannan Dhanabalan AnandaThangadurai Subramaniam Sambathkumar Ramanathan <p>To develop a simple, accurate, precise, and economical method for the simultaneous estimation of the Lamivudine and Dolutegravir in pharmaceutical dosage form by ultra-performance liquid chromatography (UPLC) using tunable ultraviolet (TUV) detector. The separation was achieved on an HSS C18 column (2.6 mm X 50 mm, 1.6 µm,) at a wavelength of 260 nm, using a mobile phase disodium hydrogen phosphate and acetonitrile (70:30 v/v) in an isocratic elution mode at a flow rate of 0.3 mL/min. The retention time for Lamivudine and Dolutegravir was found to be 1.408 min and 1.739 min, respectively. The percentage RSD of the Lamivudine and Dolutegravir was and found to be 0.8 and 0.8 respectively and the percentage recovery was obtained at 100.39% and 100.37%. The LOD, LOQ values were obtained from regression equations of Lamivudine and Dolutegravir were 0.41 ppm, 1.25 ppm, and 0.09 ppm, 0.26 ppm respectively. The regression equation of Lamivudine is y = 24270x + 12218 and Dolutegravir is y = 34783x + 1060. The developed method was found to be simple, accurate, precise, and cost-effective. The forced degradation studies indicated that the degradants and excipients are within the limit. Hence, the developed method was suitable for quantitative analysis of Lamivudine and Dolutegravir both in bulk and combined pharmaceutical dosage form.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #50 High density system for gastroretentive drug delivery system: A modern approach in dosage development 2022-01-28T14:16:55+00:00 Shubham Bhatt Heba Mazhari Anuj Pathak Nagarajan K <p>In recent decades the healthcare expand lots in disease diagnosis and their treatments will with the help of different traditional and conventional ways but due to many limitations they are not applied in the gastroretentive drug delivery system because they don’t have good gastric residence time so to overcome such problems we move on these gastroretentive drug delivery system which has desire residence time due to rate control drug release and they can be easily modified by different methods so that optimized pharmacological effects should be achieved as well. So we preferred a high-density system that is a modification of gastroretentive drug delivery system that retains the drug in the stomach with the peristaltic movement and when it gets its absorption window get easily absorbed through it. It is absorbed through the narrow window that occurs in the small intestine. These systems minimize the multiple dosing and optimize the therapeutic effect. For developing such a system we widely preferred to use the heavy materials that are inert in nature used to coat or mix with the drug moieties so that they increase the density of dosage form. They have good advantages in formulating gastroretentive drugs with limited advantages. Different evaluations parameters are also the accept pre-formulation and post compressional such as floating time, in-vitro mucoadhesion test, water uptake and mucoadhesive strength. They have improved bioavailability and are widely preferred for poorly soluble drugs at alkaline pH, drugs having less half-life and rapidly absorbed from the GI tract. There are some limitations of these systems because there is a large number of drug molecules are necessary to develop this dosage form. Different diluents such as zinc oxide, titanium dioxide, barium sulphate, iron powder, etc are used to increase the density of tablets that help to retain in the stomach for good lag time.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #51 Design, development, and evaluation of pyrazoline based mycobactin analogues as anti-tubercular agents: An in-silico approach 2022-01-29T01:04:21+00:00 Gourav Rakshit Venkatesan Jayaprakash <p>As evidenced by the WHO database, the pathogenicity and virulence of <em>Mycobacterium tuberculosis</em> have increased its infectiousness, making it a fatal disease causing a global health crisis. One of the vital health aims of the United Nations sustainable development goals is to eradicate tuberculosis by 2030. The rise in multidrug-resistant tuberculosis (MDR-TB)/ drug-resistant tuberculosis (XDRTB) cases has pushed scientists to create new chemotherapeutic agents with distinct mechanisms of action as the current medications seem to be ineffective to some extent. In this perspective, we have employed the concept of “conditionally essential target” (CET) based drug design because, over the years, mycobacteria have evolved machinery by which they can survive in the host. Therefore, it is of utmost importance to target specific enzymatic machinery that seems essential for mycobacteria’s survival. As per the current review by our research group (Shyam et al. 2021), the mycobactin biosynthesis pathway (MBP) might be a prospective therapeutic target in combating tuberculosis. <em>Mycobacteria</em> take up mycobactins (siderophores/iron chelators) when they face iron-deficient conditions, i.e., up-regulation of the MBP. This makes MBP a promising endogenous target for identifying new lead molecules. Therefore, we aim to design and develop mycobactin-mimicking compounds by retaining the structural features of mycobacterial siderophores in anticipation that it might cause inhibition of the siderophores biosynthesis enzymes resulting in the arrest of bacterial growth under iron deprived conditions. Herein, we focus on exploring pyrazoline based mycobactin analogues (non-specific mycobactin biosynthesis inhibitors) targeting MbtA enzyme (1<sup>st</sup> step of mycobactin biosynthesis). Following our prior studies described by (Stirrett et al. 2008) and (Ferreras et al. 2011), we now wish to look into the structural diversity of the previously found active compounds with a hope of finding a more potent analogue showing high affinity for MbtA (adenylating enzyme) in the in-silico exercise. Hence, we designed a small library (12 molecules) of mycobactin analogues keeping the necessary scaffold (diaryl-substituted pyrazoline (DAP)) intact and assessed their in-silico stability using molecular docking simulations (AutoDock 4.2.6) and molecular dynamics simulations (GROMACS). To find the binding modalities and inhibitory profile of the proposed compounds, they were docked in the active site of the MbtA receptor (by analogy with the homologous structure PDB ID: 1MDB). The lowest energy conformation of each docked ligand (best score) was visualized in BIOVIA discovery studio. The six top-scoring compounds were evaluated for their ADMET (absorption-distribution metabolism-excretion-toxicity) profile using SwissADME and pkCSM web server. The best molecule which revealed a good ADMET profile was taken up for MD simulation study (50 ns). Results revealed that the designed compound GV08 (-8.80, 352.58 nM), GV09 (-8.61, 499.91 nM), GV03 (-8.59, 508.51 nM), GV07, (-8.54, 553.44 nM), GV02 (-8.53, 563.30 nM), and GV04 (-8.26, 878.26 nM) had good docking score and inhibition constant. Of these GV08 and GV09 showed a good ADME profile with all major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that the protein-ligand complex is stable throughout the simulation. The future scope invalidates these findings through synthesis, characterization, and intracellular activity.</p> <p><img src="" alt="Proposed in-silico study" width="472" height="262" /></p> <p>Fig. Graphical Abstract of Proposed In-silico Study</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #52 In-silico studies of some novel benzotriazole derivatives against the NNIBP of HIV-1 RT 2022-01-29T01:15:54+00:00 Nigam Jyoti Maiti Swastika Ganguly <p>Benzotriazole is a heterocyclic molecule that has many biological actions such as antibacterial, antifungal, anticancer, anti-inflammatory, analgesic, antimalarial, and antitubercular activity. The objective of this work is to report the study of a series of designed benzotriazole derivatives that have been examined for their molecular docking in the non-nucleoside inhibitory binding pocket (Non-nucleoside reverse transcriptase inhibitors binding pocket) of HIV-1 RT. The methodology consists of a series of eight compounds (2a-h) which, based on the pharmacophoric group requirements of the NNRTIs, have been designed and drawn using ChemDraw and docked against nonnucleoside inhibitory binding pocket (NNIBP) of HIV-1 RT (PDB ID:1RT2) receptor using AutoDock Vina software. Binding mode results showed that among seven designed compounds, compound-2a{1-(4-chlorophenyl)-2-(perbromo-2H-benzo[d][1,2,3]triazol-2-yl)ethan-1-ol} gave the highest docking score of -9.3 Kcal/mole when compared to the standard Nevirapine. It also exhibited hydrogen bond interactions with PRO236 and LYS103 amino acids of the NNIBP of 1RT2. It is therefore concluded that compound 2a can be used as a lead for preparing further synthetic derivatives which can be used for docking studies in the NNIBP of HIV-1- RT.</p> <p>&nbsp;</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #53 Optimization of controlled release intramuscular formulation for antipsychotic drug 2022-01-29T01:24:23+00:00 Vishal Patel Divyang Dave <p>Presented work was aimed for optimization of poly (D,L-lactide-co-glycolide) PLGA based microsphere formulation for schizophrenia which provides 15 days sustained release for antipsychotic drug. The parenteral intramuscular route is the most preferable route of administration for efficient delivery of active substances with poor bioavailability and with a narrow therapeutic index. Schizophrenia is characterized by cycles of psychosis relapse and remission which requires a long-term treatment of antipsychotics for the prevention of relapses. As per the requirement of treatment, it is desirable to maintain drug levels in systemic circulation within the therapeutic window for a longer period. Poly (D,L-lactide-co-glycolide) (PLGA) polymers microsphere is prepared to control the release profile of anti-psychotic drug in the body. Different poly (D,L-lactide-co-glycolide) (PLGA) polymers of varying molecular weight and copolymer composition provides different release profile. Among different grades of Poly (D,L-lactide-co-glycolide) (PLGA) polymer, Poly(D,L-lactide-co-glycolide) PLGA polymer (50:50) was found suitable and further optimized during optimization trials. Biodegradable poly (D,L-lactide-co-glycolide) (PLGA) microspheres were prepared by solvent extraction and evaporation method. The release profile of the active substance is monitored for a period of 15 days in-vitro. The formulation is optimized with the use of a central composite design. During optimization trials, drug-polymer ratio, drug phase: Continuous phase ratio, and stirring speed were evaluated among formulation variables and process variables. Optimized formulations were optimized based on %entrapment efficacy, particle size distribution, burst release, day 1 release, day 7 release, and day 15 release. In-vitro releases were evaluated using bottle rotating apparatus with suitable media. In conclusion, optimized poly(D,L-lactide-co-glycolide) PLGA based intramuscular microsphere is a promising approach for controlled release injectable formulation which reduced administration frequency, increase patient compliance, increased bioavailability, prolonged therapeutic effect, minimized dose-dependent side effect, and extended-release for 15 days.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #56 Drug repurposing for the prophylaxis of Covid-19: An in-silico approach for antihistaminic drug 2022-01-29T01:29:36+00:00 Tejaswini Selwate <p>SARS-CoV-2, single-strand RNA viruses known as betacoronavirus in Coronaviridae causing the Covid-19 epidemic with high infectivity and fatality rates. The severity of the epidemic and un-attainability of highly efficacious and specific treatment for SARS-CoV-2, dire need of therapies, researchers are rushing to identify strategies to combat Covid-19 from existing labeled drugs. These already labeled and proven safety drugs can be rapidly repurposed to clinic applications for treating Covid-19 patients. In the current study, efforts were made to repurpose antihistaminic drugs, Cetirizine to combat the Covid-19 infection. The PASS study of cetirizine showed the antiviral activity of the drug. Hence the molecular docking was studied by using AutoDock Vina to find the binding affinity of cetirizine as a ligand molecule towards RDRP as an active site. The RDRP, PDB ID: 6M71, and 6TY8 (viral proteins) were selected as targets. From the docking study, the binding affinity of the drug and target 6M71 &amp; 6TY8 was found to be -7.8 &amp; -6.9 (kcal/mol) respectively. Clinical studies are needed to measure the effectiveness of Cetirizine for disease prevention, for early intervention, or as adjuvant therapy for severe Covid-19.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #57 Specific and rapid detection of Mycobacterium tuberculosis in metal complexes by RT-PCR method 2022-01-29T01:32:09+00:00 Jambulingam Munusamy AnandThangadurai Subramaniam Vijayabaskaran Manickem <p>Tuberculosis was a major public health problem and highly prevalent in India. The treatment of tuberculosis is becoming more challenging; it requires accurate and early diagnosis, screening of drug resistance, and effective directly observed therapy and short course. Metal complexes are already in clinical use and encourage further studies for new metallodrugs in the treatment of tuberculosis. With the extensive investigations on metal complexes derivatives on its anti-microbial and anti-tubercular activities, a new series of metal complexes were synthesized and tested against <em>Mycobacterium tuberculosis H37Rv</em> strain by using RT-PCR method. Salicylaldehyde (0.1 mM) was dissolved in methanol (10 mL) was added to L-Alanine (0.1 mM) followed by 2 mL of glacial acetic acid. The reaction mixture was heated under reflux for 6 h with continuous stirring. The product obtained was filtered, washed with methanol and ether. The Schiff base obtained was dissolved (0.2 g, 0.33 mM) in a mixture of ethanol-water heated to the boiling point was added to an alcoholic solution of the various metal chlorides, and refluxed for 1 h for complete precipitation. The products were filtered off, washed with ethanol and water. The synthesized metal complexes were evaluated for <em>M. tuberculosis H37Rv</em> strain by using RT-PCR method. Amplification of three target sequences from unrelated genes, namely, hsp 65 (165 bp), dnaJ (365 bp), and insertion element S 6110 (541 bp) by PCR was carried out in synthesized metal complexes and isoniazid as control. Cobalt and Zinc containing metal complexes were found to potent against the mycobacterium tuberculosis and the amplication in the RT-PCR found to be absent /negative. RT-PCR method presented as fast and precise to detect <em>Mycobacterium tuberculosis</em>. The synthesized metal complexes containing cobalt and zinc may be found to be a potent drug of choice for the treatment of tuberculosis.</p> <p><img src="" alt="" width="591" height="172" /></p> <p>Fig. Reaction</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #58 Design, development and in-silico evaluation of DENV protease inhibitors based on modification of Lai et al. potent molecule 2022-01-29T01:38:27+00:00 Sheikh Murtuja Barij Nayan Sinha Venkatesan Jayaprakash <p>Dengue has continued to affect most of the nations of the tropical and subtropical regions of the world, it has in no way given respite in the Covid era too as cases seem to be on the rise in the year 2020 and 2021. The pandemic period has imposed a significant strain on all nations’ medical infrastructure, and the emergence of dengue and the possibility of a dengue-Covid co-infection adds to the already overburdened medical infrastructure. Hence these uncertainties call for an urgent identification of antiviral drugs against dengue. DENV NS2B-NS3 protease like the HIV and HCV protease has been identified as a potential target to arrest the viral propagation as the protease plays an important role in viral multiplication. Previously reported peptide inhibitors of DENV protease to have certain limitations as the high basic residues offer pharmacokinetic challenges due to which the molecules despite being potent protease inhibitors fail to progress forward. Small molecules offer some advantages when compared to peptide inhibitors. Here we have attempted to design small molecules based on Lai et al. (2013) reported potent molecule and perform in-silico evaluation of the designed molecule to unravel the changes in the binding affinity and predict the pharmacokinetic properties. Lai et al., potent molecule had benzoisothiazole and oxadiazole scaffolds in its architecture, we modified the molecule by incorporating certain changes which included replacement of the benzoisothiazole with an oxazole scaffold while retaining the oxadiazole moiety. The newly designed ligands were docked in the available crystal structure (PDB ID 2FOM) and the binding affinities of the reference ligand (Lai et al. molecule) and designed inhibitors were compared. Further, in-silico ADMET properties of the reference ligand and top three high scoring molecules were predicted using SwissADME and pkCSM online web server. The high affinity (-7.57) of the Lai et al. molecule could be attributed to the predicted binding involving the residues of the catalytic triad (His51, Asp75, and Ser135). Amongst the ten designed ligands F2, F4 and F9 showed comparable affinities (-6.49, -6.51 and -6.67) and it was commonly seen that important predicted interactions involved hydrogen bonding, π-π stacking interactions, and π-anion interactions with at least two residues of the catalytic triad, further, after observing the interaction pattern of the reference ligand and the designed ligand it appears that the replacement of benzoisothiazole with an oxazole scaffold preserved few interactions also it was predicted that the compounds appear to be more synthetically amenable and hence the new scaffold cloud be further explored for modification The in-silico ADMET predictions further indicates towards good pharmacokinetic properties of the top designed ligands.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #59 Formulation and evaluation of antifungal emulgel using Calotropis gigantea latex 2022-01-29T01:41:55+00:00 Kalyani Dongarwar <p>Medicinal plants are an important source for the development of antifungal agents. The objective of the present study was to develop an antifungal emulgel using <em>Calotropis gigantea</em> latex extract. Emulgel comes to favor the hydrophobic drugs to give the advantage of gel. Emulgel has several advantages in the field of dermatology such as being thixotropic, greaseless, easily spreadable, easily removable, emollient non-staining, bio-friendly, transparent and pleasing appearance. Ethanolic extract of the <em>Calotropis gigantea</em> latex was tested against fungi strains. The inhibitory effect was assessed by the disc-diffusion method. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were also determined by serial dilution method. The ethanolic extract was subjected to qualitative phytochemical screening for the presence of bioactive constituents. The ethanolic extract was showed the presence of many biologically active molecules such as flavonoids, alkaloids, triterpenoids, steroids, saponins, phenols, and glycosides. The latex extract was showed a significant zone of inhibition in a dose-dependent manner. The MIC and MFC values of latex extract against fungal strains vary from 1 mg to 8 mg and the results were comparable with Fluconazole as a standard. From these results, it reveals that the latex extract of <em>Calotropis gigantea</em> possesses potent fungicidal activity along with the antimicrobial activity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #60 Success stories of drug design in drug discovery 2022-01-29T01:58:07+00:00 Shikha Kaushik Vaishali M Patil <p>Drug design and discovery in the modern era necessitates rapid and co-optimization of multiple parameters. The quality and quantity of data for drug discovery should be more predictive and accurate for respective models. There should be a holistic approach to improvise the several parameters required in drug design and discovery. Drug design approaches have been categorized broadly as rational drug design, Computer aided drug design, structure-based drug design, ligand-based drug design, or quantitative structural activity relationship. Over the past 3 decades, many new technologies also emerged like property-based drug design, ligand based metrics, cheminformatics, molecular docking, artificial intelligence, and machine learning. Multiple parameter optimization may be done effectively if we have a proper strategy and holistic approach towards drug design. The approach could include probabilistic approach, rational approach, general principles, etc. but have their own limitations in various aspects. Some approaches may increase serendipity while others may have an inaccuracy in hypothesis. Therefore, the need of the hour is to combine and leverage different approaches in order to get the best result. Some examples of successful application of drug design approaches will be presented.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #61 Synthesis and biological evaluation of some novel 1, 3, 5-triaryl-2-pyrazolines derivatives 2022-01-29T02:01:02+00:00 Subbarao Jampani <p>In the present study, 3, 4-dichloroacetophenone on condensation with different aromatic aldehydes in aqueous ethanolic solution yield corresponding chalcones. These chalcones react with phenylhydrazine obtained,1, 3, 5-triaryl-2-pyrazoline derivatives. All the prepared compounds were characterized by IR, NMR spectral data, and elemental analysis. The synthesized compounds screened for various biological activities. The compound, 2o containing a 2”-thienyl ring present at the 5<sup>th</sup> position of the pyrazoline scaffold showed good antifungal activity with MIC 2 µg/mL. The compound 2f and 2h containing 2”,4”-difluorophenyl and 4”-trifluorophenyl moieties at position-5 showed excellent antitubercular activity at MIC 1.6 μg/mL.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #63 Formulation and optimization of Famotidine mucoadhesive tablets by using central composite design 2022-01-29T02:03:58+00:00 Haranath Chinthaginjala Abdul Ahad Hindustan <p>The present study is concerned with the formulation and optimization of famotidine mucoadhesive tablets by using a central composite design. The concentrations of Cordia dichotoma dried mucilage powder (X1) and PVP (X2) were selected as independent variables. In-vitro mucoadhesion time and percentage drug release were selected as dependent variables. The model was found to be nonlinear and the curvature effect was significant. Hence, the study reported to central composite design. Tablets were prepared by wet granulation method and all the tablets prepared were evaluated for post-compression parameters. FT-IR and DSC studies demonstrated that there is no interaction between drugs and excipients. All formulations showed mucoadhesion time of 5-9 h and drug release of 96.4% to 99.69%. The results of multiple linear regression analysis were showed that a decrease in the amount of X1(CDT) and an increase in the number of X2(PVP) leads to an increase in mucoadhesion time. Contour plots were exploited to judge the association between independent variables and dependent variables. The results demonstrated the effectiveness of the proposed design for the development of famotidine mucoadhesive tablets.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #64 Methanolic leaves extract of Acacia auriculiformis Benth. cure Type 2 diabetic wounds in rats 2022-01-29T02:06:30+00:00 Naresh Kumar Rangra Kishanta Kumar Pradhan Subir Samanta <p><em>Acacia auriculiformis</em> Benth. has been traditionally known to cure various medical ailments such as sore eyes, allergy, rheumatism, and rashes. The present study was designed to confirm the wound healing efficacy of methanol leaves extract of <em>A. auriculiformis</em>. The leaves extracts were prepared in different solvents i.e., petroleum ether, chloroform, ethyl acetate, acetone, butanol, and methanol. The antidiabetic in-vitro assays were performed using α glucosidase and α amylase inhibition methods. The streptozotocin-induced diabetes model was used for 15 days study. The comparison study was carried out in diabetic wound control in respect of the period of epithelialization, % wound contraction, and hydroxyproline content in the excision wound model. However, the breaking strength parameter was used to calculate healing potential in the incision wound model. The bioactive methanol extract was subjected to LC-MS/MS analysis to characterize the phytoconstituents responsible for pharmacological activity. The methanolic leaves extract showed the highest percentage inhibition of 94.259% and 95.259% in α-glucosidase and α-amylase in-vitro antidiabetic assays, respectively. The high content of collagen fibers and stronger epithelial cells growth was observed in histopathological studies of hydrogel containing methanolic leaves extract as compared to the diabetic wound control and standard. Subsequently, for investigating the biological impact upon live cells, a cytotoxicity study was tested in different cell lines (A549, HEK293, and MCF7). Cytotoxic results showed that greater than 75% of cells were visible in all the cell lines, which gives the confirmation of the bio capability of the extract. The LC-MS/MS results revealed the presence of compounds such as β-sitosterol, lupeol, stigmasterol, and quercetin. <em>A. auriculiformis</em> is a potent medicinal plant that can be further utilized as a complementary and alternative therapy for the treatment of diabetes-induced wounds and the management of oxidative stress and diabetes.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #65 Impact of temperature and exposure on Opuntia ficus-indica and Opuntia dillenii cladode extraction on percent yield using design expert software 2022-01-29T02:11:05+00:00 Mohammad Nizamuddin Yadiki <p>The main aim of the present study is to investigate the effects of temperature and exposure time on the extraction of <em>Opuntia ficus-indica</em> and <em>Opuntia dillenii cladodes</em>. Cladodes and other parts of plants were rarely extracted for their constituents from literature. Screening, however, was not conducted to determine the influence of dependent variables on independent responses. The impact of the dependent variable on the response was determined using QbD software, namely Design Expert. A plot of <em>Opuntia ficus-indica</em> and <em>Opuntia dillenii</em> are poised, authenticated, and drenched with water to determine the effect of dependent variables (temperature and exposure time) on the response (% yield). The equation coded from this study for the percent yield was generated as +54.30+0.4061A-0.6432B+0.1500AB+0.8375A2+0.3875B2. For extraction of the contents of cladodes, 65 °C is the optimal temperature and exposure time is directly proportional.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #67 An open-source python script for QSAR study and its validation of cytotoxicity activity of thiazole analogues on MCF-7 cell line 2022-01-29T02:15:26+00:00 Prabha T Selvinthanuja C Arul Raj R Manickavalli Elangovan Sivakumar T <p>Cancer is the second leading cause of death globally after heart disease, and unfortunately, its incidence is rapidly growing. Thiazole derivatives are currently one of the most frequently studied compounds in anticancer drug discovery due to the easy optimization of the structure and the ability to synthesize a wide group of derivatives. Therefore, discovering new drugs with very high activity against the most frequently diagnosed types of cancer, as well as against those that most often lead to death, is currently the biggest challenge for many scientists. Our present study aimed to work on a trending machine learning approach with an open-source data analysis python script for discovering anticancer lead via building the QSAR model by using 53 compounds of thiazole derivatives. Dataset of 53 compounds of thiazole derivatives was collected from various reported literature and divided into train and test set compounds using the "Rule of Thumb" method. A total of 82 CDK molecular descriptors were downloaded from the "chemdes" online web server and used for our study. After training the model, we checked the model performance via cross-validation, which predicted the test set compound's bioactivity. Besides, we have applied three algorithms to forecast the model performance viz. multiple linear regression (MLR), support vector machine (SVM), and partial least square (PLS) regression model. The generated QSAR model afforded the ordinary least squares (OLS) regression as R<sup>2</sup>=0.542, F=8.773, and adjusted R<sup>2</sup> (Q<sup>2</sup>) =0.481, std. error = 0.061, reg.coef_ developed were of, -0.00064 (PC1), -0.07753 (PC2), -0.09078 (PC3), -0.08986 (PC4), 0.05044 (PC5), and reg.intercept_ of 4.79279 developed through stats models.formula module. The performance of test set prediction was done by MLR, SVM, and PLS classifiers of the sklearn module, which generated the model score of 0.5424, 0.6422, and 0.6422, respectively. In addition to this, the linear regression curve was plotted between the predicted and actual p IC<sub>50</sub> value, and all the data points mostly fell over and close to the middle line. We found that the R<sup>2</sup> values (i.e., the model score) obtained using this script via three algorithms were correlated well. There is not much difference between them and may be useful in designing a similar group of thiazole derivatives anticancer agents.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #68 Computational approach: Emerging tool in analytical research and development 2022-01-29T02:27:52+00:00 Malarvannan M Vinod Kumar K <p>We start with a short historical perspective of computational approaches in analytical research and development and discuss its current feature set. In contrast, during the development of a new chemical entity, the computational tools might be plays an important role and primed up growth. The enhancement of research and developments by the route of new or existing computational approaches minimizes the analytical work process, predicting the spectral data, spectrograms, and suitable method selection even if it doesn’t affect research work. Herein we expressed the emerging trend of new computational approaches and tools. QSRR: A software was used to predict the RT (Retention Time) by direct comparison method. Its Python program-based software and the Molecular descriptors were determined using the Mordred software package, which uses the rdkit package, Chemometrics: old and widely used in separation science, bring into play subjects such as analysis of peak asymmetry, peak overlapping, and peak optimizations. It can be done without losing sight of the analytical specificities in Chemometrics methods such as the principal components analysis (PCA), artificial neural networks (ANN), cluster analysis (CA), etc. Finally, we discussed QbD and Its role in analytical research and development.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #69 UV spectrophotometric determination of piperine content in Zandu haldi drops 2022-01-29T02:34:06+00:00 Sanjay Kumar Putta <p>Zandu haldi drops a one-of-a-kind recipe designed to improve immunity and overall health. It contains the goodness of saffron, cinnamon, cardamom, and black pepper, in addition to haldi. Hence, the present work aimed to determine black pepper in Haldi drops by UV spectroscopy with reference to the marker compound piperine. The standard curve was prepared by weighing accurately 1 mg of piperine in a volumetric flask, dissolved in methanol. Then made up the volume 10 mL with methanol to obtain a stock solution having 100 μg/mL concentration of piperine. To prepare a working standard with a concentration of 10 μg/mL, the standard stock solution of piperine was diluted. Preparation of sample solution: The test sample solution of Zandu haldi drops was made by dissolving 1ml of the formulation in methanol in a 10 mL volumetric flask. The volume was then increased to 10 mL with diluent to obtain a stock solution with a concentration of 100 μg/mL. This stock solution (1 mL) was dissolved in methanol in another 10 mL volumetric flask to yield an accurately measured quantity. To prepare a solution of 10 μg/mL, diluted the volume to 10 mL with methanol. UV Procedure: The marker compound piperine was dissolved in methanol to prepare different concentrations, i.e., 1, 2, 3, 4 and 5 (µg/mL), then the prepared formulation solution of 5 µg/mL concentration was scanned from a wavelength of 200-600 nm range, and we found the λ<sub>max </sub>at 342 nm. Then different known concentrations were monitored at 342 nm and constructed the calibration curve with the obtained results. Then the formulation was diluted with methanol and scanned at 342 nm. The scanned result of the formulation was taken as unknown and calculated from the standard concentration. The concentration of the Piperine in the formulation was 2.5%. We conclude that the formulation Zandu haldi drops contains black pepper as one of its ingredients, and its presence was confirmed with reference to Piperine by spectrophotometric method.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #71 Pullulan based electrospun nanofibers of Voriconazole: Promising preliminary studies for oral candidiasis 2022-01-29T02:39:01+00:00 Saritha Shetty Khushwant S Yadav Ritu Jain <p>Fungal infections have shown great concern with the emergence of a high threat to medically compromised patients with low immune systems, especially <em>Candida albicans</em>, with an increased incidence of resistance. For this reason, there is a need for developing innovative dosage forms. Hence, the main objective of this present investigation was to develop nanofibers of voriconazole using various polymers like pullulan and polyvinyl alcohol. The nanofibers fabricated by the electrospinning technique were characterized and optimized to confirm the ratios of the polymeric concentration, which ultimately affected the mechanical strength and diameter of the nanofibers. The optimized nanofibers were uniform, beadles, and 235±69 nm with an entrapment efficiency of 66.66±3.01%. The tensile strength of nanofibers was in the range of 14 g/cm<sup>2</sup> to 18 g/cm<sup>2</sup>. Voriconazole-loaded nanofibers indicated a modified drug release and followed a zero-order release. The anti-fungal activity of drug-loaded nanofibers exhibits superior anti-fungal activity against <em>Candida albicans</em> than plain drugs. Based on these results, they indicate that nanofibers can treat oral candidiasis and can be applied as an innovative dosage form. This innovative nanofiber system can improve patient compliance and give an effective and safe therapy.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #72 Development of novel near-infrared fluorescence probes for earlier diagnosis of AD 2022-01-29T02:44:50+00:00 Gyan Prakash Modi Himanshu Rai Rishabh Singh Gauri Shankar Sairam Krishnamurthy Sarika Gupta Saroj Kumar <p>The appearance of Alzheimer’s disease (AD) marker proteins 10-15 years earlier in the asymptomatic period makes them a versatile target for detecting and quantifying AD etiology. We aim to develop novel near-infrared fluorescence (NIRF) imaging agents for the selective detection of the pathological hallmarks of the disease, such as Aβ and tau aggregates. Early detection can help effective AD management and evaluate appropriate therapeutic interventions in preclinical and clinical studies. Advances in microscopic optical imaging techniques, especially with the aid of fluorescence molecular tomographic (FMT) imaging, reveal that fluorescent chemicals that penetrate the blood-brain barrier (BBB) and label AD markers protein with a high specificity could be evolved as a choice of interest in the near future. We designed NIRF probes using a widely preferable donor-π-acceptor (D-π-A) scaffold to develop molecular probes that efficiently penetrate BBB and label AD marker proteins. The design, synthesis, and characterization of the novel probes were carried out using the area of synthetic organic chemistry. The fluorescent properties of the developed imaging agents were calculated to determine solvatochromism and the potential for in-vivo imaging. The cell viability assay of the promising probes indicates their safer profile for in-vivo imaging purposes. Other experimental assessments like a pH stability study for 24 h revealed that these probes retain their fluorescence properties for longer with no significant decay. The lead probes were tested selectively to detect the Aβ and tau aggregates using fluorescence-based assays. The developed probes exhibited the excitation maxima in 480-540 nm and emission maxima in the range of 580 to 750 nm. The in-vitro fluorescence assay revealed that the lead probes also could selective detect Aβ and tau aggregates over BSA. We have identified I3, I8, I16, and I28 as potential leads to further investigation in the transgenic animal and Drosophila model of AD.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #74 Cholestolone: Repurposing on SARS-CoV-2 therapeutic RDRP targets 2022-01-29T03:01:48+00:00 Manish Kamble <p>Covid-19 vaccination drives are rolling out globally. However, there is a need to identify effective treatment on SARS-CoV-2 and its non-synonym variants. In pandemic urgency, discovering a new drug is impossible considering the time scale and attrition rate. Thus, the concept of repurposing labeled or already approved drugs to treat Covid-19 would be a logical choice for new drug development Covid-19. The current study identifies labeled drugs targeted to the SARS-CoV-2 therapeutic RdRp targets. The study deals with the drug repurposing using virtual screening of antilipidemic agent Cholestolone, which targets sterol regulatory element-binding protein (SREBP). The PASS study Cholestolone showed the antiviral potential. Hence, the drug was further studied computationally on RdRp targets PDB ID: 6VSB, 6XQB, and 7A98 protein sequences retrieved from the NCBI database. Molecular docking was carried out to evaluate the potential energy of interactions, hydrogen bonds, non-hydrogen bonds, and the binding mode of Cholestolon against RdRp.The docking studies were performed using AutoDock Vina to determine the potential drug candidates for inhibiting the SARS-CoV-2, and the binding affinity was found to be -6.8, -7.6, and -6.3, respectively. Based on the promising results from virtual screening, further in-vivo/in-vitro study is recommended.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #76 Simultaneous estimation of Levosulpiride and Pantoprazole in bulk and pharmaceutical formulations by RP-HPLC: Method development and validation 2022-01-29T03:05:10+00:00 Lokesh Thote <p>A simple, precise, and rapid reverse phase HPLC- SPD 20-A method has been developed and validated to simultaneously estimate Levosulpiride (LEVO) and Pantoprazole (PANTO) in a capsule dosage form. The mixture of LEVO and PANTO was separated on a C18 column (4.6 × 250 mm) using phosphate buffer: methanol (50:50) and pH seven adjusted with dilute orthophosphoric acid a mobile phase. All separations were examined at a wavelength of 254 nm with an SPD-20A UV-Vis detector operating at 210 – 400 nm wavelengths at circumambient temperature with a flow rate of 1 mL/min. The retention time of LEVO and PANTO were 2.4686 and 4.4872; respectively, the resolution was 7.3424. The developed method can be used to routine LEVO and PANTO in a capsule dosage form.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #77 Design, synthesis and characterization of disubstituted metal complex compounds of 2-(1,3-dioxoisoindolin-2-yl) acetic acid derivatives as anti-inflammatory agents 2022-01-29T03:06:52+00:00 Disha Dhabarde <p>The current investigation aimed to design, synthesize, and characterize novel anti-inflammatory drugs for superior action and reduce concomitant effects. Novel disubstituted metal complex compounds of 2-(1, 3-dioxoisoindolin-2-yl) acetic acid derivatives were designed, synthesized, characterized. The compounds were synthesized through amide intermediates. Virtual screening of synthesized compounds was checked by employing molecular docking against cyclooxygenase-II inhibitor (PDB ID: 4G7S). The compounds' structures were identified using spectral FT-IR and <sup>1</sup>H-NMR Spectrophotometer. Anti-inflammatory activity was evaluated by applying the carrageenan-induced paw edema model in albino wistar rats. The synthesized compounds showed remarkable depletion of paw edema. The percent inhibition of edema of disubstituted metal complexes of cobalt and zinc produced good anti-inflammatory activity compared to the standard drug Diclofenac.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #79 Evaluation of eugenol and curcumin in the treatment of collagen induced arthritis model of rat 2022-01-29T03:10:10+00:00 Goldi Sharma Sarwar Imam <p>Identifying common dietary substances capable of affording protection or modulating the onset and severity of arthritis may have important human health implications. A eugenol and curcumin fraction isolated from <em>Syzgium aromaticum</em> and <em>Curcuma longa</em> has been shown to possess antiarthritis in experimental animals. In this study, we determined the effect of collagen-induced arthritis in rats. The neutral endopeptidase activity was approximately 7-fold higher in arthritic joints of non-GTP-fed rats than non-arthritic joints of unimmunized rats. In contrast, it was only 2-fold more elevated in the arthritic joints of GTP-fed rats. Additionally, type II collagen-specific levels were lower in serum and arthritic joints of GTP-fed rats. Taken together, our studies suggest that eugenol and curcumin from <em>Syzgium aromaticum</em> and <em>Curcuma longa</em>&nbsp;that is rich in antioxidants may be useful in the prevention of onset and severity of arthritis.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #80 Solubility enhancement of Glimepiride by solid dispersion 2022-01-29T03:12:58+00:00 Ashish Karle Gangotri Yadav <p>Solubility is the major problem for many pharmaceutical API. Almost 40% of Drugs have solubility issues. Various techniques can enhance solubility, but solid dispersion by solvent evaporation technique is considered a cost-effective and straightforward technique. The solid dispersion of Glimepiride was prepared by using the solvent evaporation method by adding Glimepiride and carriers such as urea and PEG6000 in different ratios. The ratio of Glimepiride solid dispersion showing the highest dissolution rate was selected and formulated into tablets. Three different batches of solid dispersion were prepared by changing the drug: carrier ratio. The batch with a 1:3 ratio was found drug content 97.25 with an average particle size of 85.62 mm; also, it has the highest practical yield of 92.45 than other batches. The research work concludes that the preparation of solid dispersion of poorly water-soluble drug-like Glimepiride with suitable carriers like urea and PEG6000 increased the dissolution rate of Glimepiride and showed considerable enhancement of in-vitro and in-vivo drug release. Thus, it was concluded that the preparation of solid dispersion of Glimepiride using suitable carriers like urea and PEG6000 by solvent evaporation method is a promising technique to improve the dissolution rate of poorly water-soluble drugs. This technique was simple, cost-effective, stable, and easy to scale up.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #81 Amelioration of neurotoxicity induced by aluminium chloride, using South Indian Sitaphal, A rodent model of Alzheimer’s disease 2022-01-29T03:15:45+00:00 Sudha M Shanmuga Sundaram Rajagopal Sambath Kumar R <p>The present work is aimed to investigate the effect of ethanolic extract of fruit pulp of <em>Annona squamosa</em> against aluminium chloride-induced Alzheimer’s disease. Male Wistar rats were selected in this study and were divided into five groups (6 each). Group, I served as standard control. Group II received aluminium chloride (17 mg/kg, P.O.). Group III received rivastigmine (0.3 mg/kg, I.P.) and inducing agent (AlCl$_{3}$ 17 mg/kg, P.O.). Group IV and V received an ethanolic extract of <em>Annona squamosa</em> (200 mg/kg, 400 mg/kg, P.O. respectively) and inducing agent (AlCl<sub>3</sub> 17 mg/kg, P.O.). The rats were given respective treatment for 90 days, and behavioral parameters were determined on the 90<sup>th</sup> day. After the 90<sup>th </sup>day rats were sacrificed, biochemical and histopathological parameters were determined. Oral administration of ethanolic extract of <em>*Annona squamosa*</em> fruit pulp at doses 200, 400 mg/kg body weight showed improvement in behavioral parameters when compared to AlCl$_{3}$ induced rats, showed an increase in superoxide dismutase, catalase, reduced glutathione, and decreased levels of malondialdehyde and showed a decrease in brain acetylcholinesterase content when compared to AlCl<sub>3</sub> induced rats. The reported saturated fatty acids such as oleic acid, linoleic acids are found in animals and plants. They are primarily used to produce hormone-like substances that regulate various functions, including blood pressure, blood clotting, blood lipid levels, immune response, and the inflammation response to injury infection. The study demonstrated the beneficial effects of fruit pulp of <em>Annona squamosa</em>&nbsp;by improving biochemical and behavioral parameters.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #82 Preparation and antimicrobial evaluation of cationic lipid emulsion of flaxseed oil: A dual benefit emulsion 2022-01-29T04:26:27+00:00 Parineeta Jha Saurabh M Verma <p>Since time immemorial, nature has always been kind enough towards humanity to provide a plethora of natural resources that have always benefited humans. Most of the currently employed therapeutic agents are derived from natural sources, i.e., plants, animals, and other natural resources. Flaxseed or linseed (<em>Linum usitatissimum</em> L.) is one such annual herb that has contributed enormously to the human nutrition sector. In addition to the content of active compounds, namely omega-3, omega-6 rich oil, α-linolenic acid, α-linoleic acid, lignans, flavones, polysaccharides, alkaloids, cyanogenic glycosides, and a potential source of phenolic compounds, it also contains biologically active compounds that aid in the prevention of some chronic diseases like diabetes, CV diseases, cancers, etc. Literature also suggests using flaxseed extracts (oil/mucilage) as an antimicrobial agent. Cationic lipid emulsions provide a condensed energy source and essential fatty acids and are primarily used in parenteral nutrition (20% solution provides 2 kcal/mL). The higher concentrations have the advantage of giving higher energy value in lower fluid volume. Typically, lipid emulsions in infants and children are initiated at a dose of 1 g/kg/day and advanced by 1 g/kg/day to a maximum of 3 g/kg/day. Since lipid emulsions are derived from vegetable oils, they are also a natural source of variable amounts of vitamin K133 and E isomers. In this perspective, we aim to develop a cationic lipid emulsion of flaxseed oil and evaluate it for its antimicrobial property. This designed formulation will have both properties, i.e., providing nutrition to the user and antimicrobial activity aiding in minor microbial infections. Preparation of the lipid emulsions consists of oil suspended in an aqueous dispersion. The oil phase included: flaxseed oil, cholesterol, PEG2000, and Benzalkonium chloride (cation), while the aqueous phase included: 2.25% (w/v) glycerol for isotonicity and water (required amount). Both phases were heated to 70 °C and stirred to solubilize the components thoroughly. The oil phase was introduced to the dispersion under continuous mixing conditions and subsequently sterilized by filtration through a 0.22 mm filter device followed by storage at 4 °C for further evaluation. The prepared cationic lipid emulsion using flaxseed oil was evaluated for its physical stability, i.e., appearance, color, odor, taste, cracking, creaming, coalescence, pH, and centrifugation. Further evaluation tests like particle size, viscosity, electrophoretic properties (zeta potential), and phase separation were also carried out. Finally, the antimicrobial property of the prepared cationic lipid emulsion using flaxseed oil was evaluated using the agar well plate assay method. Antimicrobial activity was assessed against microbes like <em>Staphylococcus aureus</em> and <em>Bacillus subtilis</em> to measure the minimum inhibitory concentration (MIC) by determining the zone of inhibition. Physicochemical properties of linseed oil/flaxseed oil showed that the color of the oil is yellow-brown with a pleasant odor. The specific gravity of oil was determined to be 0.946 gm/mL. Phytochemical analysis revealed that flaxseed oil contains fats, flavonoids, glycosides, phenols, and tannins, as all tests were positive except carbohydrates. The prepared cationic lipid emulsion using flaxseed oil was physically stable as it didn’t crack and showed no creaming or coalescence upon standing/ centrifugation. The zeta potential was found to be +13.3, and the average particle size was found to be 642.0 d.nm. Variable effects were developed against <em>Staphylococcus aureus</em> and <em>Bacillus subtilis</em>&nbsp;and showed various degrees of inhibition against them. The cationic lipid emulsion of flaxseed oil has antimicrobial potential when used in high doses. At low doses, it has low antimicrobial potential. Hence, the prepared formulation is an excellent alternative medication that can deliver dual benefits to the user, i.e., treat infection caused by bacteria and provide nutrition. The future scope lies in further evaluating the formulation’s in-vitro effectiveness.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #83 Formulation and evaluation of nanoparticles with a magnetite silk core-shell for targeted drug delivery and gene therapy 2022-01-29T04:29:58+00:00 Divyansh Garg Yash Rastogi <p>This study aims to formulate and evaluate nanoparticles with a magnetite-silk core-shell for targeted drug delivery and gene therapy. Gene therapy has demonstrated considerable promise in treating a variety of disorders. Using the salting-out method with potassium phosphate (&gt;0.8 M) results in the formation of silk fibroin nanoparticles with a mean size of 475-1100 nm in a mostly process. The salting out procedure for making silk fibroin nanoparticles is displayed further. In a nutshell, potassium phosphate was added to the silk fibroin solution. The obtained particles were then kept for refrigeration for 3.5 h before a centrifuge could collect them. Increasing the silk fibroin content while adopting 1.2 M potassium phosphate (pH 7.5) might result in bigger particles. Nanoparticles are then collected into non-dispersible bunches below pH 5.5. As the formulation is still in the developing phase, delivering genes to the nucleus of the cell or cytoplasm to replace or regulate any faulty genes is necessary for effective gene therapy. However, several intracellular barriers, such as the cell membrane and endosome membrane, have considerably decreased their efficacy. As a result, carriers are required to aid in the distribution of the genes. Clinical applications require efficient and cost-effective carriers. It has been determined that due to its exceptional magnetic features, extremely low toxic effects, high biocompatibility, outstanding biodegradability, and reactive surface that may be easily changed with biocompatible coatings, targeted gene delivery systems are particularly advantageous. The capacity to target specific regions in the body and the decrease of the drug amount to achieve the desired concentration close to the target with the lowering of the drug’s concentration at non-target sites reduce the severity of the adverse toxic effects.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #84 Formulation of sustain release matrix tablet of anti-anginal drug based on Eudragid L 100-55: In-vitro drug release and kinetic approach 2022-01-29T04:34:52+00:00 Yash Rastogi Shubham Bhatt Anuj Pathak <p>This study aims to design and evaluate oral sustained release matrix tablets of BCS class 2 anti-anginal drug using Eudragit L 100-55 as the retardant polymer and mannitol as a channeling agent for the delivery of anti-anginal drug as twice-daily dose. The tablets were made using the traditional wet granulation approach. Weight variation, hardness, friability, and drug content were all determined for the tablets. The pharmacopeial requirements were satisfied by all of the formulations. In-vitro dissolution studies were carried out in 900 mL of 0.1N HCl at 50 rpm for eight hours using a USP type II device (paddle technique). The zero-order, first-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas equations have been used to investigate and describe the release profile from matrix tablets. In vitro dissolution studies found that the percent drug release dropped as polymer loading increased. The optimal composition was chosen based on solubility data comparisons with the innovator product F3 formulation (Eudragit L100-55 16% w/w of drug). The drug release profile of the optimized formulation was reasonably well controlled and homogeneous throughout the dissolving tests. As per the Korsmeyer–Peppas equation, the release of the drug of the improved formulation satisfies the Higuchi kinetic model (R<sup>2</sup> = 0.99), and the process is non-Fickian/anomalous. To conclude, the current research reveals that oral sustained release anti-anginal tablets are indeed a better choice for generating a twice-daily medication. The product’s success in-vitro dissolution studies and release pattern suggests that it should be tested in-vivo.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #85 Further structural modification in compound 2e to improve multifunctional properties for the treatment of Alzheimer’s disease (AD) 2022-01-29T04:38:45+00:00 Gourav Singh Gyan Modi Ajijur Rahaman Syed Gauri Shankar Yashpal Singh <p>One of the primary goals behind our present work is to improve further the acetylcholinesterase (AChE) inhibition property of compound 2e. The main objective of this study is to carry out further modification on the phenolic OH group of ferulic acid (FA) to improve upon the AChE inhibition activity without compromising antioxidant properties for the management of AD. We rationally selected 2e from our recent work. We modified the phenolic OH group of ferulic acid with N-(methyl or ethyl) benzyl group using a suitable linker. Next, we carried out enzyme inhibitions studies with these compounds. Further investigations such as antioxidant assay (DPPH assay), metal chelation activity, blood-brain barrier permeable assays (PAMPA assay) are ongoing with these compounds to find their potential to act as drug candidates for AD treatment. The compound (F-215) with N-methyl phenyl substitution with suitable linker on phenolic OH group of FA showed prominent AChE enzyme activity IC<sub>50</sub> = 0.92 ± 0.50 over 2e IC<sub>50</sub> = 2.42 ± 0.32 μM. The compound F-215 shows improved AChE inhibition compared to 2e. The detailed studies will be presented.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #89 In-silico docking studies of some novel benzimidazole derivatives as anti-HIV-agents 2022-01-29T04:44:26+00:00 Tushar Ranjan Mohapatra <p>Benzimidazole, a fused heterocycle bearing benzene and imidazole, has gained considerable attention from medicinal chemists worldwide. The moiety is of substantial importance because of its wide array of pharmacological activities, including but not limited to antibacterial, antifungal, anticancer, anti-inflammatory, analgesic, antimalarial, and antitubercular activity, etc. Considering the future scope of benzimidazoles against HIV, this work demonstrates molecular docking studies of a series of 7 benzimidazoles as potential anti-HIV agents. A molecular docking study was carried out on non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1 RT (PDB ID:1RT2) receptor using Autodock Vina software. From our research, it was observed that compound 2b [2-(5,6-dibromo-1H-benzimidazole)-N-(4-ethylphenyl)-acetamide] exhibited the highest docking score of -9.5 kcal/mol and was found to have strong interactions with amino acid residues via hydrogen bond interactions with LYS103 amino acids of 1RT2. Thus, in the realm of developments of benzimidazoles as anti-HIV agents, it is concluded that compound 2b can be further studied to obtain suitable anti-HIV agents.</p> <p>&nbsp;</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #91 Development of novel synthetic methodologies from aryl ketones and its application in API’s synthesis 2022-01-29T04:47:09+00:00 Shrikant Ghodse <p>There has been a very high demand for API intermediates to synthesize drugs in recent years. Carbonyl functionality is an essential precursor for drugs and their intermediates synthesis in the pharmaceutical industry. Most widely used carbonyl groups to prepare carboxylic acid, ester, aldehyde, ketones, amine, and amide APIs. We choose carbonyl ketones as a critical starting material for the synthesis of API’s Intermediate because of its stability, cheapness, ease of handling, and wide applications in pharmaceutical industries such as an excipient, reaction solvents, synthetic fiber, and medicines. We have developed simple, efficient synthetic routes for the critical heterocyclic nucleus such as 2-aminothiazole, 2-phenyl pyridine, and α-N-heteroaryl ketone. Representative drugs which contain 2-aminothiazole are meloxicam (NSAID), 2-phenyl pyridine is etoricoxib (COX Inhibitor), and α-Nheteroaryl ketone is econazole (azole antifungal). In 2020, these drugs will be commonly prescribed medication in the United States, with more than 34 million prescriptions. Results of the following invented methodologies will be presented, with their pharmaceutical applications in drug synthesis of</p> <ol> <li>2-aminothiazole from aryl ketone</li> <li>2-aryl pyridine from aryl ketones</li> <li>α-N-heteroaryl ketone from aryl ketone</li> </ol> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #92 A new class of BRCA-1 mimetics for ER positive breast cancer therapy: Design, synthesis and in-vitro screening 2022-01-29T04:50:23+00:00 Jubie Selvaraj Shyam Sundar Pottabathula <p>Inherited mutations of the breast cancer susceptibility gene BRCA1 and the frequent (30-40%) underexpression of BRCA1 in sporadic breast cancers and 46% of sporadic breast cancers show loss of one BRCA1 allele. These findings suggest that loss or functional inactivation of BRCA1 may contribute to this larger group of cancers. This study aims to find a novel class of BRCA1 mimics for Estrogen Receptor α (ERα) breast cancer that works differently from conventional antiestrogens. A novel class of hybrids with coumarin and thiosemicarbazone scaffolds was created with the premise of developing small compounds that imitate the function of BRCA-1 to regulate the ER down and inhibit the tumor activity of breast cancer cells. Using Schrodinger 2020-2, ADMET and in-silico molecular docking tests of the proposed hybrids were performed on the BRCA-1 binding cavity of ER alpha. Coumarin Thiosemicarbazone derivatives were synthesized from 7-hydroxy-4-methylcoumarin, 4-hydroxycoumarin and thiosemicarabazide with different aldehydes. All the compounds were screened for their *in vitro* cytotoxicity activity using Vero and MDA MB 231 cell lines by MTT assay. Gene expression studies were performed for Cyclin D1 and BCL2 genes by RealTime PCR using ∆∆the Ct method. The QSAR model against MDA MB 231 cell line was obtained using the multiple linear regression method and was validated by both internal and external validation procedures. IC$_{50}$ values from Cytotoxicity studies by MTT assay ranges from 5 μg/mL to 149 μg/mL. The synthesized hybrids TSCO-VI (-0.048), TSCO-XXVII (-0.217), and XXVIII (-0.214) downregulate the CyclinD1. Similarly, the hybrids all TSCO-VI (-0.628), TSCO-XVII (-0.373), TSCO-XXVII (-0.320), and XXVIII (-0.376) down-regulated the BCL2 gene. Besides, we found RMSE value=0.27760 and Correlation Coefficient (R$^{2}$)= 0.45112 in 2D QSAR by MLR method. The cytotoxicity and gene expression study findings suggest that we have found a new class of BRCA1 mimetics that works differently from conventional antiestrogens for breast cancer therapy.</p> <p><img src="" alt="" width="472" height="131" /></p> <p>Fig. Overview of the Regulatory Interplay Between BRCA-1 and ER Alpha</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #93 Wound healing activity of apple cider vinegar in association with a polyphenolic compound 2022-01-29T04:55:05+00:00 Jegadheeswari V Kaberi Chatterjee Rajdeep Saha Amirta Chatterjee Prashanta Kumar Deb Biswatrish Sarkar Papiya Mitra Mazumder <p>There is a growing concern with chronic wounds in the modern medical era because they do not heal through the usual phases in an orderly and timely manner. Bacterial colonization of <em>Staphylococcus aureus</em> is one of the major causes of chronic wounds. Generally, the wound healing process can be potentiated by increased angiogenesis. Oxidative stress also influences wound healing as it mediates degranulation and further can exaggerate the inflammation process. ACV exhibits antioxidant, anti-inflammatory, and antimicrobial activity. It has not been widely explored for its therapeutic action as a wound-healing agent. Excessive use of apple cider vinegar can cause some side effects. To reduce the overall dosage of apple cider vinegar, an attempt is being made to study the impact of apple cider vinegar associated with a polyphenolic compound. Experimentally an initial in-vitro study was performed to determine the susceptibility of <em>S. aureus</em> and <em>P. aeruginosa</em>&nbsp;against different dilutions of antibiotic Streptomycin, ACV, p-coumaric acid, ACV + P-coumaric acid were assessed. Also, an in-vitro study for the antioxidant activity of ACV, p-coumaric acid, and ACV + p-coumaric acid was evaluated and the results obtained were satisfactory. Subsequent studies are essential to conclusively show the effect of ACV in association with p- coumaric acid in wound healing which is to be carried out in the ex-ovo system to assess antimicrobial, angiogenic, and antioxidant activity and will be further evaluated along with confirmatory studies in murine models.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #94 Design, synthesis and characterization of a series of 6-substituted-4-hydroxy-1-(2-substitutedthiazol-4-yl)quinolin-2(1H)-one derivatives and evaluation of their in-vitro anticancer and antibacterial activity 2022-01-29T05:12:38+00:00 Soniya Phadte Biradar Bheemanagauda Sachin Chandavarkar Shivlingrao Mamle Desai Sanket Naik Priyanka Tiwari <p>The research work deals with the design, synthesis, and characterization of a series of 6substituted-4-hydroxy-1-(2-substituted thiazole-4-yl)-quinoline-2(1H)-one derivative [III(a-d)(1-3)] and evaluation of their in vitro anticancer activity against MDA-MB (Breast cancer) and A549 (Lung cancer) cell lines. A series of substituted thiazole-4-yl-quinolin-2(1H)-one derivative [III(a-d)(1-3)] were synthesized from starting material, substituted 4-hydroxyquinoline-2(1H)-ones I(a-d) as per the literature. Compounds I (a-d) were further subjected to condensation with chloroacetyl chloride to obtain 6-substituted-1-(2-chloroacetyl)-4-hydroxyquinoline-2(1H)-ones II (a-d). Finally, condensation with thiourea or thiamide through Hantzsch’s thiazole synthesis yields twelve derivatives of 6-substituted4-hydroxy-1-(2-substituted thiazole-4-yl)quinoline-2(1H)-ones [III(a-d)(1-3)]. The synthesized derivatives were characterized by spectral analysis. They were tested for their in vitro anticancer activity against MDA-MB (Breast cancer) and A549 (Lung cancer) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. Molecular docking studies of the synthesized compounds exhibited well-conserved hydrogen bond interactions with one or more amino acid residues in the EGFRK tyrosine kinase domain (PDB ID: 1M17) for docking study on anticancer activity. The compounds were tested for their in vitro anticancer activity against MDA-MB (Breast cancer) and A549 (Lung cancer) cell lines at 31.25, 62.5, 125, 250, and 500 µg/mL concentration using the MTT assay method. All synthesized derivatives were potent against the A549 (Lung cancer) cell line compared to the MDA-MB (Breast cancer) cell line. Compound 6-fluoro-4-hydroxy-1-(2-phenylthiazol-4-yl)-quinoline-2(1H)-one (IIIc-3) exhibited the highest MolDock score (-102.535), which was comparable to that shown by the standard Imatinib (-116.362) for anticancer docking and was found to be the most cytotoxic as compared to the other synthesized derivatives, with IC<sub>50</sub> values of 397.56 μg/mL against A549 (Lung cancer) cell line. The synthesized derivatives showed good activity compared to the standard drug and hence possessed a potential to bind with some of the residues of the active site and can be further developed into potential pharmacological agents.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #96 Significance of physico-chemical and bacteriological parameters in summation of water quality in KIET, Ghaziabad 2022-01-29T05:21:13+00:00 Prarthana Srivastava <p>Water quality is a vital concern for humanity as it is directly linked with human welfare. A parameter selection for determining water quality is totally based on the purpose of its use and the extent of required water quality and purity. With this knowledge, this paper deals with the study on analyzing drinking water parameters in a reputed educational institute situated in Muradnagar, i.e., KIET, Ghaziabad. Monthly changes in physical and chemical, and bacteriological parameters such as water temperature, turbidity, total dissolved solids, pH, dissolved oxygen, carbonate, bicarbonate, total alkalinity, hardness, calcium, magnesium, chloride,su, etc. were analyzed for a period of one year from July 2020 to June 2021. The sampling frequency was once a month. Various physicochemical parameters were selected for assessment (pH, temperature, color, odor, turbidity, total hardness, total dissolved solids, total suspended solids, chloride, fluorides, nitrates, lead, and arsenic). Moreover, the bacteriological study was recorded by finding entire coliform colonies. The results obtained were compared with WHO and EPA standards for drinking and recreational water. Except for drinking water of some floors of boys hostel that do not comply with chloride and pH standards, respectively, all other parameters were in the standard range. The present review paper depicts the importance of various parameters in reckoning water quality to check its suitability for drinking, industrial, or marine life, etc.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #97 Application of Quality by Design approach for formulation and development of mucoadhesive suppositories of Mefanamic acid for the management of high fever 2022-01-29T05:24:20+00:00 Tushar Agam <p>In this present research work, we have designed a suppositories formulation by applying a quality by design approach. We have successfully developed suppositories of mefenamic acid to meet the optimized requirement of our suppository formulation. Our main aim was to develop suppositories to target mefenamic acid via the rectal route. The fusion and molding method was used to prepare suppositories. The drug, polymer, and combined mixture of drug-polymer were evaluated for pre-formulation testing. Prepared suppositories were also assessed for content uniformity, weight variation, micro melting and micro melting, liquefaction time, and dissolution studies. From FTIR evaluation, we found no interaction between drug and polymer. For the weight variation test, all were within the acceptable range &lt;5%. Liquefaction time increased as the amount of PEG4000 &amp; PEG6000 increased and disintegrated within 4-5 min. Suppositories prepared with a combination of PEG showed a maximum release of 90% in 30 min following first-order kinetics.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #98 In-silico studies of some novel 1,3,4-oxadizole derivatives against the NNIBP of HIV-1RT 2022-01-29T05:25:54+00:00 Nisha Singh <p>Heterocyclic compounds containing the five-membered oxadiazole nucleus have a diversity of beneficial biological effects, substituted 1,3,4-oxadiazole moieties possess exciting activities such as analgesic, antimicrobial, antitubercular, anticonvulsant, and anti-hepatitis B viral activities. The main objective of this work is to report the study of a series of substituted 1,3,5-oxadiazole derivatives for their molecular docking in the non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1 RT (PDB ID: 1RT2). Here the methodology consists of 10 compounds (sn1-sn10) which, based on the pharmacophoric group requirements of the NNRTIs, have been designed and drawn using ChemDraw and docked against non-nucleoside inhibitory binding pocket (NNIBP) of HIV-1 RT (PDB ID:1RT2) receptor using AutoDock Vina software. Binding mode results showed that among ten designed compounds,compound-sn1, N-phenyl-2-((5-phenyl-1,3,4-oxadiazol-2-yl)thio)acetamide gave the highest docking score of -10.3 Kcal/mole when compared to the standard Nevirapine. It also exhibited hydrogen bond interactions with TYR-318 and VAL-106 amino acids of the NNIBP of 1RT2. The present study's finding concludes that compound sn1 can be used as a lead for preparing further synthetic derivatives, which can also be used for docking studies in the NNIBP of HIV-1- RT.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #99 Development and evaluation of mucoadhesive alginate beads of Levofloxacin hemihydrate for Helicobacter pylori treatment 2022-01-29T05:27:56+00:00 Manivasakam P Venkateswaramurthy N Kalaiyarasi C Sambathkurmar R <p><em>Helicobacter Pylori</em> (<em>H. pylori</em>) is a common bacterium it causes gastritis and peptic ulcer disease. It affects half of the world’s population. The purpose of the research work has been to develop levofloxacin hemihydrate-loaded mucoadhesive alginate beads to treat <em>H. pylori</em> infection. Formulations were prepared by ion gelation method using various concentrations of sodium alginate, carbapol 974P, and calcium chloride. The compatibility studies, percentage yield, particle size, muco-adhesiveness, surface morphology, and invitro drug release studies were evaluated. The percentage yield for levofloxacin hemihydrate-loaded microspheres was found to be in the range of 35.2±1.37% to 89.18±0.821%. The drug to polymer ratio, the entrapment, loading, and encapsulation was found to range between 79.47±0.22 to 93.1±0.62%, 36.78±0.15 to 54.48±0.25%, and 68.11±0.19 to 84.9 ±0.57%, respectively. The mucoadhesive alginate beads were spherical, discrete, and compact, and size distribution was between 4 to 24 µm. In-vitro studies showed that the drug release became more uniform in its kinetic approach towards zero order. Regards, it showed a non-Fickian diffusion mechanism. The in vitro muco-adhesiveness study revealed that all the batches of prepared beads had good mucoadhesive properties. Accelerated stability studies show no remarkable changes were observed for the best formulation. The prepared mucoadhesive alginate beads of levofloxacin hemihydrate may prolong the gastric residence time and ensure high local drug concentrations, leading to improved <em>H. pylori</em> treatment.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #101 Computational investigation of inhibitors of PIM-1 kinase triazolo-pyridazines as anticancer agents: A molecular modelling approach 2022-02-19T03:51:44+00:00 Vinayak Walhekar Ravindra Kulkarni <p>PIM kinases are members of the class of kinase family serine/ threonine kinases, which play a crucial role in cancer development. As there is no drug in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer agents targeting PIM-1 kinase. The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based drug discovery approach and structure-based drug discovery approach involving 3D-QSAR, molecular docking, and dynamics simulation. This study, association with structural properties and biological activity, was undertaken using 3D-QSAR analysis. 3D-QSAR was performed employing thirty-five molecules from the literature using Vlife Science MDS software. Molecular docking was performed using the Glide suite of Schrodinger and molecular dynamics using GROMACS software. The results of the molecular docking studies were visualized through the Maestro suite. The 3D-QSAR model was generated with the help of 35 compounds from which the best model manifested an appreciating cross-validation coefficient (q<sup>2</sup>) of 0.8866 and conventional correlation coefficient (r<sup>2</sup>) of 0.9298, respectively. Moreover, the value of the predicted correlation coefficient (r<sup>2</sup> pred) was obtained as 0.7878, respectively. The molecular docking analysis demonstrated that the analogs under study occupied the active site of the PIM-1 kinase receptor. Interactions with LYS67 in the catalytic region, ASP186 in the DFG motif, and GLU171 were noticed with numerous compounds. Furthermore, the molecular dynamics simulation study stated the ligand portrayed the strong conformational stability within the active site of PIM-1 kinase protein, forming a maximum of two hydrogen bonds until 100 ns. Overall outcomes of the study revealed that applications of the ligand-based drug discovery approach and structure-based drug discovery strategy conceivably applied to discovering new PIM-1 kinase inhibitors as anticancer agents.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #103 Comparative studies of analytical methods for simultaneous estimation of antibacterial agents in bulk and parenteral preparation 2022-02-19T03:57:09+00:00 Shruti Moon <p>To determine the comparative studies of analytical methods for simultaneous estimation of drug Meropenem and Sulbactam sodium in bulk and parenteral preparation. Literature survey reveals that techniques have been developed to estimate Meropenem and Sulbactam sodium individually. No method has been reported to evaluate Meropenem and Sulbactam sodium in combined form. Hence the above combination is selected. In the RP-HPLC process, the analyte resolved using 3.2 g of tetra heptyl ammonium bromide in a 1000 mL volumetric flask then add 400 mL acetonitrile with 44 mL of buffer solution at pH 7.0 and 4 mL of buffer solution at pH 4.0 dilute it to 1000 mL with distilled water at a flow rate of 0.6 mL/min on a gradient HPLC system containing UV-visible detector and Intersil C18 column. The detection was achieved at 230 nm. The method gives better resolution with a suitable retention time. In this method, drug determined by using a mobile phase which is ethanol: water: acetic acid (5:2:3 v/v/v) composition in TLC plate with the help of an automatic sample applicator, the plate which used was chromatographed in twin through glass chamber saturated in the mobile phase for 30 min. After a chromatographic development method, the plate was removed and air-dried. After that, separated bands on the TLC plate were scanned with the help of a wavelength range of 200-700 nm. The wavelength 230 nm had suggested for the densitometric evaluation of the separated bands, and detection was achieved at 230 nm. All strategies were confirmed in terms of accuracy and range in an analysis. The system is reliable, reproducible, selective, sensitive, rapid, economic. These analytical methods are applicable for evaluating these drugs in quality control laboratories. These methods can be suggested to estimate Meropenem and Sulbactam sodium in biological fluids.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #104 Design, synthesis and antimicrobial activity of some novel 2-phenyl, 3-substituted quinazolin-4(3H)-ones; nonclassical antifolates 2022-02-19T04:00:41+00:00 Sunil Harer <p>A new series of 2-phenyl-3-substituted quinazolin-4(3H)-one derivative was synthesized. All compounds were characterized by FTIR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, ESI-MS, and elemental analysis. Obtained compounds were evaluated for hDHFR inhibition compared to the reported drug Trimethoprim (IC<sub>50</sub>=10 µM). Primarily test compounds have produced hDHFR inhibition in the range of 4-24 µM. Docking analysis of ligands with hDHFR (PDB ID: 2W3M) has shown a hydrophobic type of strong binding interaction and confirmed the perfect fit of ligands with the active binding domain of the target protein. The possible antimicrobial activity would be by inhibition of DHFR within microbes. In-vitro antimicrobial activity was performed by agar disc diffusion method against pathogenic gram-positive strains of <em>Staphylococcus aureus</em>, <em>Bacillus subtilis</em>, gram-negative strains of <em>Escherichia coli</em>, <em>Pseudomonas aeruginosa</em> and fungi like <em>Candida albicans</em> and <em>Aspergillus niger</em>. The activity of test compounds was compared with reported standards as Gentamycin, Ciprofloxacin, and Clotrimazole. Compounds found potent antibacterial activity were QIj, QIIf (MIC=0.1-0.2 µg/mL), moderate active were QIa-d, QIl-m and QIIId, QIIIe-f (MIC= 0.5-2.0 µg/mL) and less active were Qe-I, QIk, QIn, QIIac, QIIg-h, QIIIa-c, QIIIg (MIC=2.0-3.0 µg/mL). Compounds that showed potent antifungal activity were QIc, QIIb, and QIIIf (MIC=0.1-0.2 µg/mL), moderate active were QIc-e, QIg, QIm-n, QIId, QIIIb, QIIIe (MIC=0.5-2.0 µg/mL), whereas less active were QIIa-b, QIIg with MIC=2.0-3.0 µg/mL. Functional groups attached to the quinazolin-4(3H)-one scaffold and sharing this activity would be electron-donating groups like and electron-withdrawing groups. Designed and synthesized title compounds could be fruitful in developing newer antimicrobial agents and treating deadly pathogenic infectious disorders.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #107 Insight into anti-cancer FGFR inhibitors by 3D-QSAR method 2022-02-19T04:04:56+00:00 Dharti Modh Vithal Kulkarni <p>Fibroblast growth factor receptor (FGFR) plays a vital role in tissue regeneration, angiogenesis, and embryogenesis. 3D QSAR and molecular docking methods are widely used to design new compounds to determine inhibitory activity against the biological target. In the present study, 3D-QSAR (CoMFA and CoMSIA) and molecular docking analysis were performed on 1,6-naphthyridines and pyridopyrimidines as potential FGFR inhibitors anticancer agents. 3D-QSAR was performed employing forty-one molecules from the literature using Sybyl suite, and molecular docking was performed using Glide suite of Schrodinger package. The best CoMFA and CoMSIA models were generated from test and training set derivatives with leave-one-out correlation coefficients (q<sup>2</sup>) 0.591 and 0.667, cross-validated correlation coefficients (r<sup>2</sup>cv) 0.584 and 0.652, conventional coefficients (r<sup>2</sup>ncv) 0.978 and 0.975 respectively. Both the models were validated by a test set of twelve compounds providing acceptable predictive correlation coefficient (r<sup>2</sup>pred) 0.61 and 0.68 for both models. The generated CoMFA and CoMSIA contour maps were used to design new 1,6-naphthyridines and pyridopyrimidines. Molecular docking studies indicated that compounds 75 and 29 occupied the active site of the FGFR kinase interacting with GLU520 in the catalytic region, ASP630 in the DFG motif, and MET524 in the hinge region. Collectively the outcome of the study suggested that the applications of ligand-based and structure-based approaches can be applied to discover new FGFR inhibitors as anticancer agents.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #108 Formulation of surface modified 5-fluorouracil liposomal gel anchored with Gallic acid-Stearylamine conjugate for targeted and synergistic chemotherapy for Actinic keratosis 2022-02-19T04:09:04+00:00 Rajagopalan R Senthamarai R Sanjay K Jain Piyush Trivedi <p>5-Fluorouracil (5-FU) is a potent chemotherapeutic agent frequently used in combination therapy to treat diversified cancers. However, it possesses poor permeability and a short half-life. For the first time, the synthesis of gallic acid-stearyl amine (GA-SA) conjugate combined with 5-fluorouracil (5-FU) for the treatment of actinic keratosis in A431 human epidermal carcinoma cell line by the development of surface-modified liposome-based topical gel formulations for deeper skin penetration, higher retention in targeted site and reduction in systemic toxicity. The synergistic combination of 5-FU and GA–SA conjugate in a ratio of 1:1 (1 µg/mL: 10 µg/mL) (v/v) is effectively cytotoxic against the A431 cancer cells line. Still, it is safe against HaCaT normal cell line. Four different formulations were prepared by varying the soya lecithin and cholesterol viz. 9:1, 8:2, 7:3 and 6:4 respectively. The 5-FU bearing liposomal gel was prepared, and it was then subjected for characterization to determine parameters like viscosity, spreadability, pH, and drug content. In ex-vivo skin permeation, the flux and skin deposition were determined and compared with the marketed formulation. The results of cytotoxicity activity indicate that optimized gel formulation possesses the anti-cell proliferation activity of 50% better than the plain 5-FU drug. The ability of the vesicle preparation to deposit skin was further confirmed by confocal laser scanning microscopy. The gamma scintigraphy images demonstrated that significant radioactivity was noted in the targeted area (skin) for the liposomal gel compared to the marketed one, following our distribution studies.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #111 Design, synthesis, biological evaluation and in-silico study of imidazopyridine linked thiazolidinone as promise anticancer agents 2022-02-19T04:16:09+00:00 Iqbal Md Azhar Husain Asif Alam Sanjar <p>Design, synthesis, biological evaluation, and in-silico study of imidazopyridine-linked thiazolidinedione promise anticancer agents. A series of imidazopyridine-linked thiazolidinedione rings (6a-h) were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines viz., MCF7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Two compounds 6f and 6h, exhibited remarkable results against all the three cell lines, but the compound 6h was found to be the most active against breast cancer cell lines. Amongst all the synthesized compounds, 6h displayed the highest antioxidant results. Further, potent compounds 6f, and 6h showed no signs of toxicity at a dose ranging from 50 to 500 mg/kg of body weight of animals. Biochemical parameters (SGOT and SGPT) of compound 6h have nearly matched the control in hepatotoxicity studies. Molecular docking &amp; MM-GBSA dG bind studies agree with the outcome of in vitro anticancer and antioxidant activities. The most potent compound 6h, was found to have the highest docking score, binding energy, and ADME parameters, which are in the acceptable range. Thus, it could be concluded that 6h, an imidazopyridine derivative endowed with the thiazolidinedione ring system, has the potential to be developed as an anticancer agent.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #112 Design and development of tea tree oil niosomal gel for bacterial infection 2022-02-19T04:39:24+00:00 Gangotri Yadav Ashish Jain <p>Tea tree oil is a yellow liquid extracted from <em>Melaleuca alternifolia</em>. It has an excellent antibacterial, antifungal, anti inflammatory activity, which is used topically in niosomal gel for bacterial infection. Tea tree oil-loaded noisome was prepared by thin-film hydration technique. Nine different batches are prepared by changing cholesterol: span 60 ratios, hydrating speed, and hydrating time. All batches were evaluated for entrapment efficiency; batch F8 had the highest entrapment efficiency of 73%. An optimized batch was selected to prepare niosomal gel by dispersion method using carbopol, propylene glycol. Different batches of the gel prepared by changing the concentration of carbopol and formulated gel were evaluated for various parameters like homogeneity, grittiness, pH, drug content, spreadability, in-vitro drug release. The cup plate method was used to check the antibacterial activity against different microorganisms. The drug and formulation were tested against <em>Staphylococcus aureus</em> and <em>Candida albicans</em>. Out of all batches, TTNG6 was found more effective with drug content 75.34%, Spreadability 58.12, pH 7.01, viscosity 10324 cps. Tea tree oil optimized niosomal gel was found more stable with good antibacterial properties than conventional gel.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #113 Identification of newer hits as potential FAK inhibitors using in-silico methods 2022-02-19T04:43:06+00:00 Sahaya Nadar Tabassum Khan <p>Focal adhesion kinase (FAK), a protein tyrosine kinase, has been overexpressed in cancer cells and plays a pivotal role in the proliferation of tumor malignancy. There is no FDA-approved and marketed the drug as FAK inhibitor for clinical use by far. This calls for a dire need to advance an area of active FAK inhibitors as possible anticancer entities. In the present study, applying appropriate filters in the ZINC database, 631 compounds were selected and virtually screened using Autodock Vina in PyRx 0.8. Further, Lipinski’s Rule of Five (Ro5) was applied on the best hits identified through molecular docking studies to find their drug-likeness using SwissADME. The compounds were further screened for their toxicity by Pro Tox II. Our analysis identified four hits, compounds ZINC95595125, ZINC43200601, ZINC40395224, and ZINC95593660, which exhibited an excellent binding score along with passing the ADMET evaluations making these ligands a primary choice to be tested experimentally. The identified hits displayed good crucial interaction with the FAK enzyme (PBD ID: 2ETM) and can be considered as potential leads. Further in-vitro and in-vivo anticancer activity against selected cell lines in which FAK are overexpressed can be carried out for these identified compounds.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #114 Formulation and evaluation of floating microspheres of Levofloxacin hemihydrate for the treatment of H. pylori infection 2022-02-19T04:50:04+00:00 Neelamegarajan R Venkateshwaramurthy N Kalaiyarasi C Sambathkumar R <p>More than 80% of peptic ulcer diseases are caused by <em>H. pylori</em>&nbsp;infection. The purpose of the study was to formulate and evaluate the floating microspheres of Levofloxacin hemihydrate to treat <em>H.pylori</em>&nbsp;infection. The floating microspheres of Levofloxacin hemihydrate were prepared by emulsion solvent diffusion technique using HPMC K100M, EC used as polymers. SEM, drug entrapment efficiency characterized the formulation; In-vitro Buoyancy Studies performed up to 12 h. In-vitro drug release and accelerated stability studies. The mean diameter of the microspheres was found to be in the range of 191.1–214 µm. The drug entrapment efficiency of the prepared microspheres varied from 49.35% to 69.25%. The percentage of buoyancy for this system was 74.61±1.4. The In-vitro buoyancy studies showed that most microspheres floated for around 9 h. In-vitro drug release achieved 80% in 12 h. Accelerated stability studies showed that formulation was stable. The prepared floating microspheres of Levofloxacin hemihydrate formulation, the drug-loaded microspheres had high floating time, and prolonged-release may provide more availability of the drug in the stomach. It may provide effective treatment against <em>H. pylori</em>.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #116 GC-MS fingerprinting and in-vitro biological evaluation of hydroalcoholic extract of Rosemary officinalis Linn. leaves 2022-02-19T04:54:33+00:00 Nithya S Prabha T Srimyvizhiy Marappan Jagadeeswaran Murugesan Sasikala S <p><em>Rosmarinus officinalis</em> Linn. is an aromatic perennial herb with fragrant evergreen needle-like leaves. It is member species of the Lamiaceae family. It is used commercially for antispasmodic, antimicrobial, anti-inflammatory, analgesic, antipyretic, cardiac tonic, antioxidant, antiapoptotic, anti-tumorigenic, antinociceptive, antiasthmatic, and neuroprotective properties. Our study focuses on GC-MS phytochemical analysis and biological evaluation of hydroalcoholic extract of <em>Rosemary officinalis</em> along with its bioassay-guided fractions viz. n-hexane and chloroform through in-vitro anti-inflammatory and antimicrobial activity. Using the solvent, hydroalcoholic extracted the Rosemary leaves via triple kinetic maceration process. Then, the obtained mother tincture of the hydroalcoholic extract was subjected to bioassay-guided fractionation using various polar and non-polar solvents such as chloroform and n-hexane. Hydroalcoholic extract's phytochemical nature and its two fractions from <em>Rosemary officinalis</em> were confirmed by its spectral and chromatography analysis through UV-Vis and GC-MS. Hydroalcoholic extract and its two fractions of Rosemary leaves were evaluated for their in-vitro anti inflammatory and antibacterial activities by using various doses of 150, 250, 350 mg/kg against gram-positive (<em>Staphylococcus aureus</em>, <em>Bacillus subtilis</em> and <em>Pseudomonas aureus</em>) and gram-negative (<em>Klebsiella pneumonia</em>, <em>Escherichia coli</em>, and <em>Proteus vulgaris</em>) bacteria by agar plate diffusion method. Our study results revealed that the phytochemical screening through UV-Vis and GC-MSanalysis of hydroalcoholic extract of Rosemary leaves showed the presence of flavonoids, alkaloids, tannins, sterols, terpenes, and saponins. Further, the hydroalcoholic (HA), chloroform (CH), and n-hexane (NH) extract on in-vitro anti-inflammatory activity showed noteworthy inhibition viz. HA: 28.77%, 51.69%, and 75.49%, CH: 32.54%, 55.32%, and 78.42%, NH: 25.68%, 49.51%, and 66.82% at various doses, respectively, which was compared with standard drug Indomethacin (10 mg/kg). In addition, in-vitro antimicrobial studies showed significant inhibition on both gram-positive and gram-negative bacteria at (CH:1000 µg/mL, HA: 500 µg/mL, NH: 250 µg/mL). Our present study revealed that the chloroform fraction of <em>Rosemary officinalis</em>&nbsp;Linn possesses good antimicrobial and anti inflammatory activities compared with the hydroalcoholic and n-hexane extracts. This promising result may be due to the rich flavonoid content in chloroform extract. However, further study is required to know the complete mechanism of these extracts on the inflammatory process and use these extracts for life-threatening problems like cancer and tuberculosis is under process.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #118 Impact of fasting on systemic inflammation in periodontitis in mice 2022-02-19T05:07:48+00:00 Karan Singh Vinay Kumar <p>Periodontal disease is the most common chronic inflammatory illness in humans, affecting the teeth’ supporting connective tissue and cementum, bone resorption, leukocyte infiltration, and periodontal pocket formation, such as the gum or gingival tissues the periodontal ligament. Periodontal disease is the most prevalent chronic inflammatory disease in humans, and its incidence has been increasing over the past decade. Fasting has been performed for millennia and has a role in adaptive cellular responses that reduce oxidative damage and inflammation, improve energy metabolism, and strengthen the cellular defense of the periodontal region. The current study was planned to investigate the impact of fasting regimens in improving periodontal health and ameliorating various oral and systemic inflammatory conditions in mice. Periodontitis was induced via ligature silk wire in mice. The parameters assessed were bone loss, lipid peroxidation, and inflammatory markers. This study applied an intermittent fasting regimen (every other day fasting) for four weeks. The levels of pro-inflammatory markers (e.g., IL-2, IL-6, IL-1β, TNF-α, IFNγ, and CRP) and oxidative stress were increased in the serum samples of periodontal disease mice. The fasting regimen in these animals significantly decreased the serum inflammatory markers and lowered free radical production. This regimen showed less bone loss than the non-fasting groups at the ligature-periodontitis site. The study results showed that fasting could be beneficial for preventing bone loss and systemic inflammation in periodontitis.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #119 In-silico assessment of gyrA obtained from fluoroquinolone-resistant urinary isolates of E. coli 2022-02-19T05:10:40+00:00 Venkatesh Kamath Kanav Khera Venkat Earny <p>Urinary Tract Infection (UTI) is one of the most common infections affecting the human race. Although it is prevalent in the female gender, it also affects men. <em>Escherichia coli</em> are one of the most common culprits causing UTI in 90% of the cases. Ciprofloxacin and other fluoroquinolones have been successfully used to treat UTI caused by <em>E. coli</em>. However, this bacteria has obtained Multiple Drug Resistance (MDR) against more than one fluoroquinolone class by horizontal transfer of genes. Most of this MDR occurs by alteration of the gyrA genes. This study examines the mutation of gyrA within the quinolone-resistance determining region (QRDR) of the resistant <em>E. coli</em> isolated from the urine of the UTI patients. This study also involves the molecular docking of ligands on the fluoroquinolones to examine their binding efficacy and effect on the resistant strains. Understanding the correlation between genetic determinants of pathogenicity and phenotypic antibiotic resistance is key to preventing the spread of resistant bacterial strains, especially in specific population groups based on hospital antibiograms and analysis of prevalent resistant strains. To validate this, 50 urinary isolates of <em>E. coli</em>&nbsp;were analyzed for resistance towards fluoroquinolone antibiotics. The resistant strains were chosen based on their definite resistance to at least two fluoroquinolones (Ciprofloxacin, Norfloxacin, Ofloxacin, Levofloxacin). Genomic DNA extraction was carried out after strain characterization, and isolates showing a 260/280 ratio within 1.6-1.9 were labeled pure. Primers were designed to target a mutation hotspot, Quinolone resistance determining region (QRDR), in the gyrA gene. As confirmed by AGE, the synthesized oligonucleotides were used to run a PCR assay to amplify a gene target spanning ~350bp. The PCR products were purified using a spin-column format, and the purified amplicons were subject to single direction reads of Sanger’s sequencing technique. 25% of the samples were sequenced. The data suggested that mutations in amino acid residues 83 and 87 were prevalent in the chosen population and parallel studies of similar scope.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #121 Synthesis of green nanofiber mat for tissue engineering applications 2022-02-19T05:16:45+00:00 Aditya Dev Rajora Trishna Bal <p>Tissue engineering is the discipline that deals with the regeneration of damaged tissues. Nanofibers are the most acceptable substances for the regeneration of tissues because it mimics the extracellular cellular matrix (ECM), so the cells can quickly proliferate on it. Natural polysaccharides are used to develop nanofibers because of their biocompatibility and biodegradability. But certain limitations are also associated with these natural polysaccharides, such as low mechanical property, so chemically derived polymers are also incorporated with the natural polysaccharides to overcome this limitation. Nanofibers can be procured using various techniques; electrospinning is the most favored technique. This perspective aims to explore the combination of polyvinyl alcohol (PVA) and neem gum (NG) to fabricate nanofibers using the electrospinning technique. Various nanofibers were prepared by varying the concentration of PVA and NG. The preparation of nanofibers was confirmed using multiple analytical methods. The antimicrobial activity of PVA, NG, and PVA/NG nanofiber was investigated against bacteria such as <em>Staphylococcus aureus</em> and <em>Escherichia coli</em>&nbsp;using the disk diffusion method. Nutrient agar media was used for the incubation of bacteria. The NG and PVA/NG nanofiber can inhibit the growth of bacteria. This suggests that the nanofiber will provide a framework for the proliferation of cells and can treat the infections caused by bacteria.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #122 A Molecular docking study for antiasthmatic targets of Manilkara zapota (L.) P. Royen leaves in treating asthma 2022-02-19T05:19:55+00:00 Mansi Agrawal Papiya MItra Mazumder <p>Asthma is a chronic reversible allergic inflammatory disease of lung airways that affects millions of people worldwide; even then, only symptomatic treatment is given to control asthma. At present, the low dose inhaled corticosteroids are the standard gold treatment for asthma but have many severe side effects. So, this study aimed to search for a natural potent anti-inflammatory therapeutic agent that reverses this inflammatory disease with fewer side effects. In this, <em>Manilkara zapota</em> (L.) P. Royen is a medicinal plant, majorly rich in polyphenols. All the more, leaves of <em>Manilkara zapota</em> (L.) In traditional medical practice, <em>Manilkara zapota</em> (L.) P. Royen has been used to treat diseases like fever, hemorrhage, cough, and cold. In addition, previous pharmacological studies have found antioxidant, anti-inflammatory, antitumor, and antiarthritis bioactive properties. Still, no scientific data is available regarding the antiasthmatic profile of the leaves of <em>Manilkara zapota</em> (L.) P. Royen. In this study, phytoconstituents rich in polyphenols present in <em>Manilkara zapota</em> (L.) P. Royen leaves were docked with different asthmatic targets like ß-2 adrenergic receptor (PDB ID: 2RH1), leukotriene receptor (PDB ID: 6RZ6), NFк-B receptor (PDB ID: 1A3Q) via software AutoDock Vina 1.1.2. Molecular docking results revealed that Apigenin-7-rhamnoside exhibited a high affinity of -8.2 kcal/mol for the ß-2 adrenergic receptor (PDB ID: 2RH1) selected target among the studied compounds compared to standard control Formoterol with binding energy -6.4 kcal/mol. Thus, Apigenin7-rhamnoside, a flavonoid, is present in <em>Manilkara zapota</em>&nbsp;(L.) P. Royen leaves could be predicted possible as a bronchodilator agent for treating asthma. Therefore, in this experiment, an attempt was made to identify a natural potent antiasthmatic agent with the help of molecular docking, if validated in the wet lab, which could be used to treat asthma with less severe adverse effects.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #123 Formulation and characterization of Ternary amorphous solid dispersions for solubility enhancement of an antidiabetic drug 2022-02-19T05:23:28+00:00 Muralidhar Pisay Srinivas Mutalik Koteshwara KB <p>The current study aimed to prepare the stable amorphous solid dispersions (ASD) and effervescence solid dispersions (ESD) of the poorly water-soluble Glibenclamide (GLB) and to enhance its solubility and physical stability. For this purpose, Kollidone VA 64, PEG-3350, and Gelucire 50/13 were selected as water-soluble carriers. The miscibility of the drug and carrier was predicted by molecular dynamics simulation studies, Hanson solubility parameters, Flory Huggins theory, and Gibb’s free energy. Solid dispersions were prepared by microwave, solvent evaporation, lyophilization, and Hot melt extruder (HME) methods. The prepared ASDs and ESDs were subjected to solubility and dissolution studies and other characterization studies. The in-silico and theoretical approach suggested that the selected polymers might exhibit better miscibility with the GLB. All solid dispersions had shown improved solubility and dissolution rate. But solid dispersions prepared with Kollidone VA64 and HME proved better solubility and dissolution. The solid-state characterizations like FTIR, $^{1}$H NMR proved the formation of intermolecular hydrogen bonding between the drug and carriers, which was comparatively more in ESDs than ASDs. Thermal analysis, PXRD, microscopic examination of GLB, ASDs, ad ESDs confirmed that the drug has converted to the amorphous form, which was more in ESDs than ASDs. Gibb’s free energy concept suggested that the prepared solid dispersions were stable at room temperature for 90 days. Ex-vivo intestinal absorption study on optimized ESDs designed by Kollidone VA64, HME technique exhibited higher flux and permeability coefficient when compared to pure drug suggesting better drug delivery. Amorphous solid dispersion and effervescence solid dispersions technology greatly enhanced Glibenclamide solubility, dissolution rate, and stability. Further, this might exhibit better bioavailability confirmed by an ex-vivo intestinal absorption study.</p> <p><br><img src="" alt="" width="472" height="93"><br>Fig. 3D-structure of GLB, Gibb’s free energy plot, and drug release plot</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #124 Preparation and evaluation of Glibenclamide tablet using soyalecithin as a lubricant and as a solubility enhancer 2022-02-19T05:30:01+00:00 Joel Joshua J Punitha S Tamilarasi S <p>The literature review reveals that soyalecithin is used as a lubricant and increases poorly soluble drugs' solubility. The present investigation was undertaken to prepare a glibenclamide tablet using soyalecithin as a lubricant and a solubility enhancer. Microcrystalline cellulose is added as disintegrant-magnesium stearate, a lubricant. Pre and post-compression studies were compared. Glibenclamide is sulphonylurea which is used in the treatment of Type II Diabetes Mellitus. It has poor solubility (BCS class II). Soya lecithin is added to enhance solubility. Formulations were made by direct compression. The drug and excipients were mixed by geometric dilution method and passed through 100# mesh sieve. The mixture was compressed in an electrically driven rotary tablet punching machine (Cadmech mini-press) using 11/32 punch to obtain tablets. The weight of the tablet was maintained at 200±5 mg. The observed benefits of using soya lecithin as a direct compression vehicle resulted in faster and greater release of the drug, reduced excipient use, reduced cost and time of manufacture, and revealed the potential use of soy lecithin as a substitute of lubricant and solubility enhancer in directly compressed tablets of glibenclamide. The post-compression studies were conducted (for formulations F 1, F 2, F 3, F 4, F 5, and marketed product) and the results were tabulated and compared. All the formulations passed the weight variation test, friability test, and hardness test. The results of the disintegration test revealed that formulations F 1, F 2, F 3, and F 4 show fast disintegration compared to F5 and marketed products. Dissolution studies were carried out for 30 min. The results are shown and compared. It shows the formulations which contain soya lecithin release, i.e., above 90% of the drug within 30 min. The observed benefits of using soy lecithin as a direct compression vehicle resulted in faster and greater release of the drug, reduced excipient use, reduced cost and time of manufacture, and revealed the potential use of soy lecithin a substitute of lubricant and solubility enhancer in directly compressed tablets of glibenclamide.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #125 Benzohydrazide schiff base derivatives: Design, synthesis, spectroscopic study and antimicrobial screening 2022-02-19T05:35:33+00:00 Afrin Ansari Savita Tauro Sahaya Nadar Pradnya Patil <p>This research project aimed to design and synthesize hydrazide schiff base derivatives as an antimicrobial agent. Thus the objective was to perform in-silico studies of the designed compounds, synthesize, accomplish spectral analyses, and assess in-vitro antimicrobial activity. In-silico physicochemical properties using Molinspiration Cheminformatics software and computational toxicity studies with software, ProTox II was gaged for anticipated compounds. A four-step synthetic pathway was executed by both traditional condensation and microwave-assisted synthesis. Structural elucidation was conducted using Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (<sup>1</sup>H &amp; <sup>13</sup>C-NMR), and mass spectroscopic studies of synthesized samples. Eventually, these derivatives were tested in-vitro against six bacterial strains (gram-positive: <em>Bacillus subtilis</em>, <em>Staphylococcus aureus</em> and gram-negative: <em>Escherichia coli</em>, <em>Salmonella typhi</em>, <em>Klebsiella pneumonia</em>, and <em>Pseudomonas aeruginosa</em>) with agar disc diffusion assay method and determined the area inhibited by these organisms (Zone of inhibition values). A total of fifteen of the twenty proposed compounds were synthesized, with ten derivatives moving forward for further research. Spectroscopic analyses such as IR, NMR, and mass spectroscopy aided in the structural elucidation of ten synthesized compounds, with their results reported in tabular form. Antimicrobial tests revealed that the compounds were highly effective against MTCC <em>E. coli</em> and <em>S. typhi</em> strains. Both of these microbes exposed substantial activity against IVb and IVj. <em>E. coli</em> and <em>S. typhi</em> were significantly inhibited by IVe and IVf, respectively. Conclusion: Consequently, substituted benzohydrazide Schiff bases were fruitfully designed, synthesized, and analyzed. In-vitro antimicrobial activity of the compounds indicated the potential of hydrazide Schiff bases.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #126 Preparation and evaluation of Diltiazem hydrochloride transdermal patches using film casting technique 2022-03-14T15:58:11+00:00 Pradheep S Asma P Tamilarasi S <p>The present investigation develops controlled release matrix type transdermal patches of diltiazem hydrochloride using natural and biodegradable polymer hydroxyl propyl methylcellulose. Any type of formulation that allows a drug substance to transit from outside of the skin through the layers of skin to underlying tissues and finally into the systemic circulation to exert a pharmacological action is called a transdermal drug delivery system. Dose of diltiazem hydrochloride 180-240 mg daily, melting point 210-215 °C, and overall drug lipophilicity make the drug suitable for transdermal drug delivery system. Transdermal patches were prepared by film casting technique. 73.96 g of Diltiazem hydrochloride and HPMC in the ratio of 3%, 4%, and 5% were dissolved in ethanol and chloroform (1:1 mixture) and castor oil 30% w/w of polymer used as a plasticizer. The mixture was poured into a glass plate using a ring of 4.3 cm diameter having 5 mL capacity. After drying at room temperature for 24 h, circular film of 1 cm diameter (area of 0.785 cm<sup>2</sup>) each containing 4 mg drug was cut. The prepared formulations were evaluated for their physical characteristics such as percentage moisture absorption, thickness, weight, and drug content. The physico-chemical evaluation data revealed that percentage moisture absorption is high in formulation F6 and low in formulation F2. Thickness and weight uniformity were in the range of 0.036±0.004 to 0.040±0.006mm and 0.024±0.005 to 0.045±0.003 mg, respectively. The drug content was found to be 90.3±0.050% to 93.1±0.071% in the prepared delivery system. In vitro drug release revealed that the formulation F1, F2, F3, F4, F5, and F6 releases 77.05%, 73.22%, 68.59%, 67.07%, 59%, 48.41% of the loaded drug at the end of 24 h from the formulations, respectively. The formulation F5 containing 4% HPMC as drug reservoir of diltiazem hydrochloride and EC 5% as rate-controlling membrane has shown best release at the end of 24 h in a concentration-independent manner. In conclusion, formulation F5 achieved the targets of the present study, such as: Reducing the frequency of administration and no systemic side effects. Hence it may improve patient compliance.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #127 Preparation and optimization of Tinidazole loaded transferosomal gel 2022-03-14T16:06:31+00:00 Snehal Kurhe <p>The aim of the present study is to formulate and optimize a tinidazole-loaded transfersomal gel. Transfersomes are formed by self-assembly of non-ionic surfactant and soya lecithin upon hydration with an aqueous medium resulting in a lamellar structure that encapsulates both polar and non-polar drugs. It is also a vesicular carrier for drug delivery systems. In the present research work, we prepared tinidazole transfersome using a non-ionic surfactant, span 60, and soya lecithin in a ratio of 80:20 concentration by the thin-film hydration method. These prepared tinidazole transfersomes were then incorporated into a gel which was prepared by varying concentrations of poloxamer 407. Evaluation of prepared transfersomal gels done by homogeneity, grittiness, spreadability, extrudability, drug content, in-vitro diffusion, and stability study. In this experiment performed transferosomal suspension was dispersed in carbomer and Poloxamer gel, a tinidazole transferosomal gel was created for Bacterial Vaginosis. After evaluation of both the gels, Tinidazole transfersomal gel having poloxamer as the gelling agent was found to have greater in-vitro drug release 90.41% along with the highest R2 value among all the formulations and good stability for shelf life. Tinidazole Transfersomal gel formulation provided sustained and prolonged delivery of Tinidazole in controlled manner with constant release as it follows zero-order release kinetics. The optimized formulation of transfersomal gel containing tinidazole is quite simple and stable.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #128 Cerebral ischemic conditioning responses: Exploring the potential mechanisms for post stroke neuroprotective benefits 2022-03-14T16:10:02+00:00 Abhimanyu Kaushik Himanshu Aggarwal Kanishk Luhach Pallavi Jain <p>Ischemic stroke is a commonly encountered and severe symptom of cerebral ischemia and other cerebrovascular disorder. It is a condition characterized by the rapid onset of cerebral injury resulting due to rupturing or obstructed blood supply in the brain. Stroke every year claims approximately 5 million lives globally and renders the same number bedridden with severe morbid states. Stroke is a heavy contributor to the socio-economic burden on families and the healthcare economy. On the other hand, stroke is rare in persons under the age of 40, and when it does occur, it’s usually due to excessive blood pressure. Unfortunately, pharmacological therapeutic choices are limited, and they are commonly unsuccessful during the preoperative period. Improved therapeutic results in patients necessitate novel techniques; thus, techniques like ischemia preconditioning (IPC) and ischemic postconditioning (iPoCo) were developed to reduce the severity of the injury. The impact of IPC and iPoCo on learning and memory function is widely investigated in rats and mice via a battery of behavioral, biochemical, and molecular methods. Ischemic preconditioning (IPC) is a process in which a sub-threshold ischemic shock to an organ activates cellular pathways that can assist in decreasing damage caused by later severe ischemic events. This finding implies that ischemic preconditioning (IPC) is a protective response to a potentially harmful stimulus like hypoxia, ischemia, inflammation, or hypoglycemia. Short episodes of ischemic reperfusion after a more severe type of ischemic shock to an organ are called ischemic postconditioning (iPoCo). The ischemic state induces several biochemical changes in the brain, and neuronal death follows. These changes are visible and can be evaluated by Branes task (Branes Circular Maze), Neurological Evaluation (Spontaneous activity, Symmetry in the movement of four limbs, Forepaw outstretching, Climbing, Body proprioception, Response to touching vibrissae), Elevated plus Maze Test, Sucrose Preference Test, Forced Swim Test, Social Interaction Test, Morris Water Maze Test, Open Field Test, Paw Pressure Test, Novel Object Recognition Test (NORT). We employ these models to close the pre-clinical research and clinical treatment gap.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #129 Targeting central cannabinoid receptors for exploring their potential ischemic preconditioning like 2022-03-14T16:17:33+00:00 Pallavi Jain Abhimanyu Kaushik Himanshu Aggarwal Kanishk Luhach <p>Ischemic stroke is a chronic debilitating condition having co-morbidities running in parallel. Stroke can be referred to as a state of hypoperfusion of any organ, brain, and heart suffer the most as they are most sensitive to ischemic and hypoxic insults. Extensive research has shown that transient, sublethal ischemic episodes condition these cells and prevent them from the severe episodes of ischemia. But the limitation of this method is the unpredictability of stroke occurrence. Moreover, there are not many palliative approaches for the management of stroke. The need for better therapeutic outcomes to reduce the severity of the disease results in the development of new pharmacologically efficacious models like ischemic pre-conditioning and Ischemic post-conditioning. Ischemic preconditioning benefits arise in response to brief episodes of ischemia followed by a prolonged state of ischemia and subsequent restoration of the blood supply. IPC makes the cerebrum more resistant to upcoming ischemic insults. Ischemic post-conditioning is a technique in which repetitive periods of occlusion of vessels at the onset of reperfusion diminish reperfusion injury, proceeding to prolonged ischemic effects. We have identified that the pathways up and down-regulated during IPC coincide with the cerebral pathways modulated by cannabinoid receptors. CB receptors are found predominantly in the cortex, which plays a crucial role in learning, cognition, and locomotor movements. Based on our hypothesis, we have designed these studies to explore the potential of cannabinoid receptors in cerebral ischemic preconditioning responses in mice and to induce transient sub-lethal Ischemic preconditioning episodes. They evaluate the ischemic preconditioning benefits of cannabinoid receptor modulation using a battery of behavioral and biochemical methods. The methods that will be covered in this study include: Morris water maze test, Rota-rod test, Lateral push test, Inclined beam test, and Neurologic severity scores-estimating biochemical methods like TBARS, GSH, CAT, AChE, SOD, TTC staining, etc. Therefore, we can conclude that ischemic preconditioning and postconditioning exert a neuroprotective effect and are somehow associated with reducing infarct size.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #133 Curcumin in-situ gel for the local treatment of periodontitis: Preparation, in-vitro evaluation and clinical assessment 2022-03-14T16:21:47+00:00 Himansu Bhusan Samal Itishree Jogamaya Das Lavanya Boyeena Niranjan Patra Sreenivas S A <p>Periodontitis is one of the most widespread oral inflammatory infectious diseases affecting the oral cavity. This study aims to develop and characterize a more effective syringeable curcumin in-situ gel to treat Periodontitis and evaluate its clinical effectiveness. Curcumin in-situ gel was formulated by the cold method using temperature-sensitive (Poloxamer 188, 407), pH-sensitive (Carbopol 934P), and ion-sensitive (Gellan gum) polymer. Gel formulations including Poloxamer 407 and Carbopol 934P as independent factors for the selected response like viscosity and gelation temperature were optimized using central composite design (CCD). The formulation evaluations were made to ascertain drug content, gelation temperature, viscosity, stability, and in-vitro drug release. Appropriate physical characteristics for most formulations and their suitability for periodontitis were observed. Appropriate gelation temperature ranged from 30.2 to 36.5 °C, with a pH of 6.14 to 7.25. The viscosity of the gel at 40 °C ranged from 12540 to 32400 centipoise. In all cases, the designed formulations were successfully syringeable with a 21-gauge needle at cold temperature. Most of the formulations showed a greater correlation with the Higuchi equation, supporting the assumption that diffusion was the primary mechanism of drug release. Clinical study of the optimized gel formulation revealed a substantial reduction in the clinical markers of periodontitis. The study shows that Curcumin in-situ gel may be considered a promising delivery for the safe and efficient treatment of periodontitis which substantially overcomes the drawbacks of conventional therapy.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #135 Potential TLR-4/MD-2 complex antagonism initiated bacterial asthma exacerbation treatment 2022-03-14T16:29:03+00:00 Swamita Arora Sangeetha Gupta Sanjar Alam <p>To optimize the animal model of asthma through TLR4 receptor antagonism mechanism as bacterial infections frequently cause asthma exacerbation. TLR4 responds to bacterial stimulation, putting toll-like receptors (TLRs) at the frontline of our microbial defense. This study showed how TLR4 stimulation and TLR4/MD2 complex inhibition were utilized for AHR allergic asthma management in a mouse model. Swiss albino mice were induced with the administration of PBS, LPS, and ovalbumin; later, two compounds activated the TLR4 receptor underlying mechanism for asthma induction. It was 23 days protocol in which animals were sensitized (i.p). It challenged intranasally (i.n.) and treatment given on the 21<sup>st </sup>&amp; 22<sup>nd</sup> day followed by euthanasia and samples (BALF &amp; lungs tissues) collected on day 23<sup>rd</sup>. Further analysis such as TLC/DLC &amp; lung histopathology of asthma parameters in toxic &amp; treatment groups compared to the standard group was performed. Bronchial smooth muscle hyperplasia and goblet cells swelling developed in poisonous groups. The bronchoalveolar lavage fluid (BALF) analysis demonstrated a significant increase in inflammatory infiltration and bronchial architectural damage. In contrast, bovine serum albumin delivery causes allergic airway irritation. The bacterial asthma exacerbation caused by LPS drug rise was decreased by treatment with a TLR4/MD2 complex inhibitor, which significantly reduced cell inflow in BALF. The airway-stabilizing action of TLR4 antagonist drugs suggests that TLR4-MD2 problematic inhibitor drug shown positive therapeutic potential compared to standard medications and could be used to treat microbial-induced allergic asthma exacerbations in the future.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #136 Design, synthesis and evaluation of novel heterocyclic derivatives for anti-tubercular activity 2022-03-14T16:44:23+00:00 Amol Bansode Hemant Kumar Jain <p>Tuberculosis (TB) is a major global health problem that causes morbidity and mortality in developing countries. TB is one of the significant causes of death worldwide from single infectious agents after covid19, ranking above HIV/AIDS. It is estimated that one-third of the entire human population is infected with this disease. In 2020, there were an estimated 1.3 million deaths among HIV-negative people, increasing from 1.2 million in 2019 and an additional 214000 deaths among HIV-positive people, a slight increase from 209000 in 2019. TB affects people of both sexes in all age groups, but the highest burden is in men (aged ≥15 years), who accounted for 53% of all TB cases in 2020. Multi-drug resistance (MDR) and extensively drug resistance (XDR) is associated with the current Tb treatment. Hence, it is essential to develop new heterocyclic compounds to overcome this problem and be more targeted to <em>Mycobacterium tuberculosis</em>. A small library of novel ethyl 1, 2, 3, 4-tetrahydro-6-methyl-2-oxo-4-phenyl pyrimidine-5-carboxylates 5 (m-t) was synthesized using the Biginelli reaction. IR, NMR characterized synthesized compounds, and mass spectral analysis followed by evaluation for in-vitro anti-tubercular activity against <em>Mycobacterium tuberculosis</em>&nbsp;(Mtb) H37Rv strain (ATCC27294) using microplate Alamar blue assay (MABA). Among the title compounds, 5m, 5n, 5o, 5q showed more potent activity (MIC 1.6 µg/mL), compounds 5p and 5s were equipotent (MIC 3.12 µg/mL), while compound 5r showed moderate activity (MIC 6.25 µg/mL). In comparison, compound 5s were found less potent (MIC 100 µg/mL) when compared to standard drugs Pyrazinamide, Ciprofloxacin, and Streptomycin. Also, all the synthesized compounds were evaluated with In-silico molecular docking studies against dihydrofolate reductase (DHFR) enzyme with PDB ID:1DF7 and showed a high G-score compared to standard drugs.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #138 Investigation tripeptides as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphate 2022-03-14T16:47:26+00:00 Tanya Goyal Nagarajan Kandasamy Anjleena Malhotra <p>Tuberculosis is ubiquitous, the 13<sup>th</sup> underlying cause of death &amp; the second significant communicable disease after Covid-19. Antibiotic resistance is the chief obstruction in the treatment of <em>Mycobacterium tuberculosis</em>. To accomplish prevention from extensively drug-resistant &amp; multi-drug-resistant TB peptides with minor side effects, high potency against Mycobacterium protein tyrosine phosphatase-B (mPTPB) is in demand, which is chosen as a target for our study. mPTPB is pivotal for Mtb intracellular survival, resulting in decreased macrophage apoptotic activity and demolition of an innate immune response, leading to reduced secretion of inflammatory cytokines IL-6. We aim to study detailed docking-based investigations of tripeptides against mPTPB as potent inhibitors with more negative docking scores based on ΔG value compared to standard cefsulodin. Through preliminary drug-like filters of Lipinski rules and Molinspiration, five tripeptides (PRO-ARG-CYS, ARG-CYS-LYS, ARG-CYS-GLY, ARG-CYS-ALA, ARG-CYS-MET) were selected out of 154 tripeptides. Swiss DOCK online tool was used for docking using mPTPB as target (PDB ID: 1C83) with HP Laptop having Intel Core i5 processor with 8GB Ram and 64-bit operating system. Among the results obtained, ARG-CYS-LYS was found to be the most promising lead as a potent mPTPB inhibitor with a ΔG value of -9.08 kcal/mol in comparison to Cefsulodin (ΔG value = -11.54 kcal/mol) followed by ARG-CYS-MET (ΔG value = -9.04 kcal/mol), PRO-ARG-CYS (ΔG value = -8.50 kcal/mol), ARG-CYS-GLY (ΔG value = -8.43 kcal/mol) and ARG-CYS-ALA (ΔG value = -8.33 kcal/mol). These results indicate that ARG-CYS-LYS can be considered an excellent therapeutic agent against mPTPB.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #139 Microemulgel containing Nigella sativa oil and berberry extract for treatment of hypo pigmentation. 2022-03-14T16:51:39+00:00 Pranali Badhe Harshala Baviskar Ashish Jain Jeeja Pananchery Karishma Dhanawade Praful Jain Prachi Kharate <p>Formulate and evaluate microemulgel for skin pigmentation, containing a combination of <em>Nigella sativa</em> oil and Berberry extract. <em>Nigella sativa</em> oil is rich in thymoquinone, and berberry extract contains berberine. The solubility studies of nigella oil and berberry extract were conducted to select surfactants and cosurfactant. The pseudo ternary phase diagram was constructed based on the chosen oil and combination of surfactant and co-surfactant (Tween80 and propyleneglycol 400) at different ratios (1:1, 2:1, 3:1, 4:1, 5:1, 6:1). The microemulsion was assessed for globule size, zeta potential, pH value. The microemulsion was incorporated into a 1% carbopol 934 gel base and evaluated for spreadability, viscosity, drug release, drug content, and tyrosinase activity. The stability study of the optimized formulation was carried out as per ICH guidelines. A zero-order drug release mechanism was exhibited by microemulgel. The optimized microemulgel showed good stability for three months at accelerated conditions. The average globule size was 185.5 nm, the zeta potential was 0.4 mV, and drug permeation was 90.22% and 88.62% for berberine and thymoquinone, respectively, within 24 h. The tyrosinase activity results showed that a combination of berberry extract and <em>Nigella sativa</em> oil act as a tyrosinase accelerator. The optimized microemulgel formulation containing <em>Nigella sativa</em> oil and berberry extract is a stable and promising skin darkening agent.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #140 Formulation and optimization of Levofloxacin hemihydrate thermosensitive otic in-situ gel for the treatment of otitis media 2022-03-14T16:59:00+00:00 Onkar Markunde <p><em>Otitis media</em> is a middle ear infection that clears within a week but requires repeated administration of the drug. Topical available marketed solution when instilled, rapidly eliminated from ear cavity if the patient had not kept the head inclined. To overcome the issues related to the conventional drop, in the presented study, Levofloxacin hemihydrate was incorporated in a poloxamer-based temperature-sensitive otic in-situ gel system to prolong the duration of action, better patient compliance, greater convenience, and ease of administration. Levofloxacin hemihydrate temperature triggered in-situ gelling system was prepared by the cold method using poloxamer 188, Poloxamer 407 alone or in combination with bioadhesive polymers like Natrosol 250M, HPMC K4M, and Klucel HF in variable ratios. On the basis of primary evaluation, 32 factorial design was applied (Design Expert 13 software from Stat Ease Inc., USA) to investigate the combined influence of two independent variables (X1-poloxamer; X2-HPMC K4M) on dependent variables (Y1-gelation time, Y2-gelation temperature, and Y3- drug release). Based on the factorial design, nine formulations were prepared, and response values Viz. gelation time, gelation temperature, and drug release were studied. The selected formulations were further characterized for suitability using pH, viscosity, spreadability, and drug content. Statistical validation of all batches was carried out using ANOVA provision in the software. Optimization by graphical and numerical methods was carried out by fixing maximum and minimum responses for each factor and response. The software suggested nine batches showed gelation time 30±1.0 sec - 300±1.00 sec, gelation temperature 35.33±1.15 °C - 47.66±0.7 °C and drug release in between 92.20±4.12%-99.70±3.02%. The response surface plot and counterplot of nine experimental runs on each response suggested that gelation time, gelation temperature, and drug release were decreased when the concentration of poloxamer 407 and HPMC K4M was increased. This may be due to an increase in pseudoplastic and viscoelastic behavior of poloxamer 407 and increased swelling characteristics of viscosity generating hydrophilic polymer HPMC K4M. An optimized batch containing poloxamer 20% and HPMC K4M 0.5% showed observed responses were close to values predicted by the optimization technique. The optimized batch had a gelation time of 52.33±1.15 sec, gelation temperature 34.33±1.15 °C, and in-vitro release 96.42 ± 3.72%. The 32 factorial design was found to be suitable for the development of an otic in-situ gelling system. Optimized Levofloxacine hemihydrate otic in-situ gel formulation can be used in topical application for <em>Otitis media </em>management.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #141 Development and optimization of Eberconazole loaded niosomes using central-composite design 2022-03-28T15:58:34+00:00 Priyadarshi Aparajay Abhimanyu Dev <p>The study aims to develop and optimize eberconazole (EBZ) loaded niosomes using Central-Composite Design and their preliminary evaluations. EBZ loaded niosomes were developed using ether injection method containing gelucire 48/16 (Nonionic surfactant) and cholesterol as an additive agent. These formulations were statistically optimized using the Central composite experimental design. Leica microscopy and FESEM microscopic studies have been conducted to evaluate the surface morphology of developed niosomes. Dynamic light scattering technique has been used to determine the particle size, polydispersity index, and zeta-potential. The dialysis bag and centrifugation method have been used to determine the optimized formulation’s entrapment efficiency and release profile.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #143 Design, synthesis, induced-fit docking, DFT, molecular dynamics, and biological evaluation of some thiazolidine-4-ones as antidiabetic agent through PPAR-γ partial agonism 2022-03-28T16:03:09+00:00 Subham Das Alex Joseph <p>Diabetes is a metabolic disorder that affects roughly 463 million people, with the number expected to climb to 700 million by 2045. The most frequently observed adverse effects of antidiabetic drugs (e.g., thiazolidinedione) are weight gain and hepatotoxicity. This study aims to synthesize a series of novel thiazolidine-4-one ring-bearing molecules with improved antidiabetic activity with lesser side effects. Thiazolidine-4-one derivatives were synthesized using suitable synthetics scheme and characterized by IR, NMR (<sup>1</sup>H and <sup>13</sup>C), mass spectroscopy, and elemental analysis studies. Synthesized compounds were then subjected to pharmacological evaluation as antidiabetic agents (OGTT, HbA1C) along with toxicity studies. Their unique selectivity toward the PPAR-γ was investigated using molecular modeling techniques (Molecular docking, ADMET, and molecular dynamics). All the synthesized compounds showed moderate to excellent antidiabetic activity. One synthesized compound 4h demonstrated an excellent antidiabetic activity by reducing blood glucose levels compared with the standard drug (Pioglitazone). It was encouraging to note that all the tested compounds have displayed no significant liver toxicity due to the partial activation of the PPAR-γ receptor. In molecular docking studies, compound 4 h shows hydrogen bond interaction with SER342 amino acid, an essential feature for PPAR-γ partial agonism, and retains the same binding during 100 ns molecular dynamics study. Compound 4h is less toxic, according to histopathology studies of the organs and regular body weight monitoring. Structural activity relationship study also reveals that the presence of the bulkier ring system significantly improves the antidiabetic activity. It can be concluded that the synthesized compound 4h has the potential for further development as a safer antidiabetic agent with fewer side effects.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #144 Pharmacological investigation of antimicrobial, analgesic and antiinflammatory activity of Physalis angulata L. fruit extract in experimental animal model 2022-03-28T16:07:18+00:00 Rasmita Jena Diptirani Rath Durga Madhab Kar <p><em>Physalis angulata L.</em> (Solanaceae) is an indigenous medicinal herb that has been recommended for fever, sore throat, pain, malaria, asthma, cuts, wounds, obstructive urination, diabetes, cancer, earache, etc. The research aimed to screen the phytoconstituents and evaluate the toxicity profile, antimicrobial, analgesic, and anti-inflammatory activity using various experimental animal models. Air-dried fruit powder sample was defatted with petroleum ether and extracted with methanol using the Soxhlet apparatus. Again the samples were macerated with distilled water to obtain the aqueous extract. The phytochemical screening was performed as per the standard methods. Antimicrobial activity was assessed by the agar well diffusion method using microbial strains like <em>B. cerues</em>, <em>E. coli</em>, <em>S. aureus</em>. Healthy Swiss albino Wistar rats of either sex weighing 180-200 gm were selected for this experiment as per the approval of the Institutional Ethics Committee. The acute oral toxicity was performed as per the OECD guidelines 423 to evaluate the safety profile of the extracts. The analgesic and anti-inflammatory activity were studied at two different doses (200 mg/kg and 400 mg/kg body weight) in the different models using Wistar albino rats. The crude extracts confirmed the presence of alkaloids, steroids, flavonoids, phenols, saponins, tannins, glycosides, etc. 400 mg/kg body weight was found to be safe for oral administration. In the antimicrobial study, methanol extract showed the highest zone of inhibition against the tested <em>S. aureus</em> (29 mm), and aqueous extract showed the least inhibition. The results revealed that only 400 mg/kg of methanol extract has statistically significant (p &lt; 0.05) analgesic activity in the hot-plate model and tail-flick model. The higher dose of methanol extract significantly decreased the no. of writhing in the acetic acid-induced writhing model. 200 mg/kg and 400 mg/kg body weight dose of methanol extract had significant anti-inflammatory activity in terms of %inhibition of paw edema in carrageenan model compared to aqueous at 3 h and 4 h. Hence, the herb <em>P. angulata</em>&nbsp;<em>L.</em> might be considered as a budding candidate for bioactivity-guided isolation of natural anti-inflammatory and analgesic agents.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #145 Formulation and evaluation of orodispersible tablets of Trimethobenzamide HCl 2022-03-28T16:12:12+00:00 Sakshi Garg Lakshmi <p>Orodispersible drug delivery system has shown bioavailability of drug significantly greater than conventional drug delivery system and dissolves rapidly in saliva without the need of water. Trimethobenzamide HCl is an anti-emetic drug and acts within the central nervous system to inhibit the medullary chemoreceptor trigger zone by blocking emetic impulses (dopaminergic) to the vomiting center. The present research work was an attempt to develop orodispersible tablets of Trimethobenzamide HCl with the aim of rapid therapeutic effect with good mouth feel and to enhance patient compliance. The preformulation studies included FTIR, and DSC of the drug was carried out to study the behavior of the drug. The drug excipient compatibility showed no significant interaction between drug and excipients used in the formulation. The tablets were formulated by wet granulation method using Crosspovidone as a super disintegrant and Poly vinyl pyrrolidine as a binder to provide faster disintegration and drug release. 32 full factorial design was performed to study the effect of the formulation variables (Crosspovidone and Mannitol) on disintegration time. Tablets were evaluated for their morphology, micromeritics properties, drug content, wetting time, water absorption ratio, disintegration time, and dissolution studies. Numerical optimization was performed to find the optimum composition, and based on this; an optimized formulation was selected. Optimization studies showed that the extra design check point formulation (F10) matched closely with optimized formulation (F3) with a similarity factor of 96.89%. Kinetic studies for in vitro drug release followed Korsmeyer’s–pepp as a model. Disintegration time of optimized formulation was found to be 26 sec with 99.51% of drug release within 15 min. Finally, it was concluded that the developed orodispersible tablets for Trimethobenzamide HCl could be a promising system for rapid action, good mouth feel as well as better patient compliance.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #146 Development and characterization of geniste in nano structured lipid carriers loaded topical nanogel to target melanoma cells 2022-03-28T16:15:41+00:00 Lakshmi Sanjay Singh Surabhi Soni <p>The aim of the present study was to develop topical nanogel utilizing genistein loaded nanostructured lipid carriers (GEN-NLCs) in order to provide a controlled release and targeting skin epidermis. The different batches of GEN-NLCs were prepared by solvent diffusion method using orthogonal Taguchi optimization design. Then, GEN-NLCs were evaluated for various physicochemical parameters like particle size, zeta potential, entrapment efficiency, and in-vitro drug release studies. Morphological studies were performed using scanning electron microscopy and atomic force microscopy. Moreover, in-vitro anticancer studies and cellular uptake studies by fluorescence microscopic studies were performed on A-375 melanoma cell lines. GEN-NLCs loaded gels were prepared utilizing methocel and characterized for particle size and texture profile analysis (TPA). Further, the optimized gel was evaluated for in-vitro and ex-vivo occlusion test, in-vitro release study, ex-vivo human skin permeation &amp; retention study. GEN-NLCs were found to be in the nanometric range with 89.50% entrapment efficiency and -14.98 mV zeta potential. Release studies confirmed the controlled release nature of the NLCs. In-vitro anticancer activity by MTT assay revealed that the nanoparticles were found to be 15.37 times more effective against melanoma as compared to the drug, whereas fluorescence studies confirmed enhanced cellular uptake with time. The results of the evaluation of gel indicated that there is no significant change in the texture profile of hydrogel after incorporating GEN-NLCs having 3% of methocel gel. GEN-NLCs loaded gels showed an occlusion factor almost 3.45 times higher than control gel at the end of 24 h resulting in a significant increase in the occlusivity of the hydrogel. In-vitro release kinetic data of Genistein exhibited the sustained release of drug which follows Higuchi release kinetics ex-vivo studies further confirmed a decrease in flux across the skin, i.e., controlled release pattern of GEN from hydrogel and increased hydration and retention in the epidermis. Topical delivery of GEN-NLCs loaded gel showed a potential delivery system to target skin epidermis for melanoma cancer.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #148 In silico ADME and toxicity prediction of resveratrol derivatives for DPP-4 inhibition activity: Molecular docking study 2022-03-28T16:25:08+00:00 Shipra Singhal Surya Prakash Singhal Vaishali Patil <p>Out of the various therapeutic targets available for diabetes mellitus (DM), dipeptidyl peptidase4 (DPP-4) inhibitors are found to be the safest, effective, and tolerable target. They act naturally to control blood glucose levels and improve nephropathy, retinopathy, and cardiovascular complications. Some phytoconstituents such as cirsmaritin (IC<sub>50</sub> = 0.43±0.07 μM), hispidulin (IC<sub>50</sub> = 0.49±0.06 μM), naringenin (IC<sub>50</sub> = 2.5±0.29 μM) (Bower A. M. et al. 2014), resveratrol (IC<sub>50</sub>, 0.6±0.4 nM), luteolin (IC<sub>50</sub>, 0.12±0.01 μM), apigenin (IC<sub>50</sub>, 0.14±0.02 μM), and flavone (IC<sub>50</sub>, 0.17±0.01 μM), curcumin, erysenegalensein E were identified as strongest DPP-4 inhibitors. Present work aims to evaluate the ADME, toxicity, drug likeliness prediction, and docking studies of some resveratrol derivatives for their DPP-4 inhibition activity. Computer-aided toxicity and pharmacokinetic prediction studies attracted the attention of pharmaceutical industries as an alternative means to predict potential drug candidates. In the present study, in-silico pharmacokinetic properties (ADME), drug-likeness, toxicity profiles of thirty resveratrol derivatives as DPP-4 inhibitors for antidiabetic activity were examined using SwissADME, Pro Tox II, Way2Drug, vNN, and ADMET lab web tools. The drug-likeness prediction results showed most of the compounds obey Lipinski’s rule of five for their drug-like molecular nature. Further, molecular docking studies of these compounds were performed on the DPP-4 subunit and compared with natural DPP-4 inhibitors. Docking studies have led to the conclusion that there are some identical amino acid interactions as TYR666 and TYR662, seen in both synthesized compounds and natural DPP-4 inhibitors. This study completely gives a good scope for further derivatization and optimization of synthesized compounds to get clinical candidates as DPP-4 inhibitors for antidiabetic activity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #149 Improvement in solubility of poorly soluble Bosentan monohydrate through self micro-emulsifying drug delivery system 2022-03-28T16:28:43+00:00 Sainath Yede <p>Self micro-emulsifying drug delivery system (SMEDDS) is a transparent, physically stable micro-emulsion with a droplet size of less than 50 nm. In the presented study, solubility of bosentan monohydrate (BM) was improved by formulating SMEDDS using oils, surfactant, co-surfactant and to improve the stability; the optimized formulation was converted into a solid dosage form. Initially, the saturation solubility of BM in oil (sesame oil, arachis oil, olive oil, soyabean oil), surfactants (Tween80, Tween20), co-surfactant (PEG200, PEG600) was determined, and those indicating the highest solubility of BM were selected. From the solubility studies, a different combination of components of the emulsion was selected as Group A: sesame oil, Tween20 and PEG; Group B: sesame oil, Tween80, PEG200; Group C: arachis oil, Tween80 and PEG200; Group D: arachis oil, Tween20 and PEG600. The surfactant and co-surfactant were blended together (Smix- 1: 1,2:1, 3:1, 4:1 ) and the oil:Smix (9:1, 8:2, 7:3, 6:4, 5:5, 4:4, 3:7, 2:8, 1:9) were titrated with distilled water till a clear solution was obtained. The pseudo ternary phase diagrams were constructed (Chemixsoftwere) to study micro emulsifying capacity and the effect of the drug on phase structure. The optimized batch was converted into solid SMEDDS by physically mixing with Aerosil 200 in variable concentration. The optimized batch was incorporated in capsule dosage form, and a stability study was carried out. The saturation solubility of BM was found to be superior in arachis oil and sesame oil; surfactant Tween80 and Tween20; co-surfactant PEG600 and PEG200. Amongst all the studied formulations, batch S11 containing sesame oil (10%), Tween80 (13.4%), and PEG200 (6.6%) with Smix 2:1 (90%) showed Nephelometric turbidity unit of 19, the droplet size of 35.77 nm, PDI of 0.169, Zeta potential –21.61 and in-vitro drug content of 88.57% and was considered as most suitable and highly efficient SMEDDS. S11 was converted into a solid-state by mixing physically with Aerosil 200. The homogenized batch S-S11 having S11 and Aerosil 200 in 1:1 ratio (batch S-S11) showed good flow properties and released 88.57% BM in 60 min. Batch S-S11 was found stable for three months during stability study at 40±2 °C and 75±5% RH.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #150 Design, synthesis and evaluation of 5-substituted-2-amino-1,3,4-thiadiazole derivatives as anticancer agents 2022-03-28T16:31:40+00:00 Rangan Mitra Dipika Singh Senthil Raja Ayyannan <p>The present work is aimed at designing, synthesizing, and evaluating a library of 2-amino-1,3,4-thiadiazole based compounds as anticancer agents through their inhibitory action against Cyclin-Dependent Kinase (CDK2) enzyme. CDK2 is a member of the protein kinase family, which plays a major role in regulating various events of the eukaryotic cell division cycle. It is overexpressed in cancer cells, resulting in abnormal regulation of the cell cycle and hyperproliferation. Thus, CDK2 is regarded as a potential therapeutic target for cancer therapy. The 2-amino-1,3,4-thiadiazole nucleus is a privileged scaffold in drug discovery due to its diverse biological activity. One of its derivatives, 2-(4-fluorophenylamino)-5-(2,4 dihydroxyphenyl)-1,3,4-thiadiazole (FABT, 1), was shown to inhibit the extracellular signal regulated kinase pathway to induce cell cycle arrest in human non-small lung carcinoma cells (NSCLC). A series of compounds containing the 1,3,4 thiadiazole scaffold was designed through molecular hybridization of FABT (1) with the experimental tyrosine kinase inhibitor Semaxanib (2). The designed compounds were synthesized by conventional methodologies and characterized by NMR and IR characterization techniques, followed by evaluation for their antitumor activity against C6 neuroblastoma cell line by MTT assay with doxorubicin as the reference standard. Molecular docking of each synthesized compound was done in the active site of CDK2 (PDB ID: 4LYN) using AutoDock4.2, and the binding energy was calculated. A library of compounds having general structure 3 (as shown in Figure 1) has been designed, synthesized, and evaluated for CDK2 inhibitory potential. The most potent compound of the series (compound 4) is shown to inhibit CDK2 with an IC$_{50}$ of 0.005 µM. It shows binding energy of -9.62 kcal/mol when docked with CDK2 active site (PDB ID: 4LYN) and interactions with PHE82, LEU183, ILE10, ALA31, LEU134, VAL164, ALA144, and GLU81 residues and pi-pi interaction with PHE82 and LEU83.On the basis of the above findings, it can be postulated that this rigid scaffold 3 could serve as a template for the design of potential drug candidates in cancer therapy by modulating CDK2 activity.</p> <div class="page" title="Page 76"> </div> <p>Fig. General Structure of Library Compounds</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #151 Formulation and evaluation of floating tablets of Levofloxacin for eradication of Helicobacter pylori 2022-03-29T13:20:01+00:00 Jaganathan K Sambathkumar R Venkateswaramurthy N Vijayabaskaran M <p><em>Helicobacter pylori</em> (<em>H. pylori</em>) infection is a common worldwide infection and an important cause of peptic ulcer disease and gastric cancer. The purpose of the study was to prepare levofloxacin (LVF) floating tablets for <em>Helicobacter pylori</em> eradication. Floating tablets of Levofloxacin were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose (HPMCK4M, HPMCK100M) and natural polymers like xanthan gum, guar gum in an optimized ratio. The floating property was achieved using an effervescent mixture of sodium bicarbonate and citric acid (3:1). Hardness, friability, content uniformity, floating time, and floating lag time of the prepared floating tablets were evaluated. The Physical properties, drug content, floating time, and drug release behavior of prepared tablets was assessed. In-vitro results showed that Levofloxacin (LVF) floating tablet formulation composed of synthetic and natural gum shows a longer drug floating time character. The formulation contains both synthetic and natural gum shows a longer floating time (&gt;12 h). From the study, it can be concluded that a combination of hydroxypropyl methylcellulose (HPMCK4M, HPMCK100M) along with natural polymers can be used to increase the gastric residence time of the dosage form to improve the local effect of Levofloxacin for the treatment of <em>H. pylori</em>&nbsp;infection.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #152 Design and characterisation of green tea catechin loaded biodegradable nanoparticles 2022-03-29T13:25:20+00:00 Itishree Jogamaya Das Himansu Bhusan Samal <p>Catechins, an herbal polyphenolic flavonoid found in green tea, have received considerable attention due to their favorable biological properties, including cardioprotective, neuroprotective, and anti-cancer effects. The aim of the present work is to develop biodegradable polymeric nanoparticles based oral drug delivery for encapsulation and controlled release of polyphenol compound Catechin. Catechin nanoparticles were prepared using biodegradable polymer Poly-ε-Caprolactone (PCL) by Solvent Diffusion technique using TPP as cross-linking agent. SEM analysis showed that the nanoparticles were smooth and the average particle size of the optimized formulation is 218.7±0.579 nM. The Zeta potential showed incipient stability for the best formulation. FTIR and DSC showed no significant interactions between catechin and Poly-ε-Caprolactone after encapsulation and cross-linking. Results showed a substantial change in the release rate and in the percentage entrapment of Catechin from nanoparticles formulations. The percentage yield of all the nanoparticles showed a good yield. The highest drug entrapment efficiency (90.73%) and in-vitro release (91.87%) were obtained with the optimized formulation (CTC5). The prepared Catechin-loaded nanoparticles proved to be promising dosages form with improved bioavailability.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #153 Synthesis and anticancer evaluation of some Novel 4-thiazolidinedione derivatives 2022-03-29T13:28:15+00:00 Kritika Sachan Wal Pranay Iqbal Md Azhar <p>A thiazolidinedione (TZD), also known as a glitazone, is a five-membered carbon ring molecule commonly used to treat Type 2 diabetes and insulin resistance. There have also been numerous prospective studies that have confirmed these compounds’ anti-proliferative efficacy, despite side effects such as hepatotoxicity, water retention, and cardiac complications. We have synthesized 12 new TZD analogs where the N-heterocyclic ring is directly connected to the thiazolidinone moiety to reduce their toxic properties. By adopting a widely applicable synthetic method, eleven TZD derivatives were synthesized and tested for their antiproliferative activity in MTT and assessed for their in-vitro cytotoxicity potential against selected human cancer cell lines, namely PC-3, A549, and MCF-7 (breast cancer) cells. Among this new series, compound 19e was found to exhibit a promising cytotoxic effect against the triple-negative breast cancer cell line (MDA-MB-231) with an IC$_{50}$ value of 0.97±0.13 μM. Decreased cellular viability and migration, as revealed by Western blot analysis, part of this antiproliferative effect was supported by apoptosis studies evaluating BCL-xL and C-PARP protein expression. Our data highlight the promising potential of these TZD derivatives as antiproliferative agents for the treatment of prostate and breast cancer. A series of new β carboline hybrids have been synthesized and assessed for their in vitro cytotoxicity potential against selected human cancer cell lines, namely PC-3, A549, MG-63, HCT-15, MDA-MB231, A431, and PANC-1, along with a normal human cell line (L-132). Among this new series, compound 19e was found to exhibit a promising cytotoxic effect.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #155 Synthesis, characterization and molecular docking study of some quinoline based Schiff’s bases as potential Eg5 inhibitory agents 2022-03-29T13:32:50+00:00 Shankar Alegaon Venkatasubramanian U Rohini Kavalapure <p>In Search of novel Eg5 inhibitory agents, new series of quinoline-based Schiff bases molecules were designed, synthesized, and their structures were elucidated using FTIR, <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, and mass spectral analysis. The newly synthesized compounds were evaluated for their Steady-state ATPase and Malachite Green Assays. The results of Malachite Green Assay revealed that compound 2((7-chloroquinolin-4-yl) amino)-N’-(4-formylbenzylidene) benzo hydrazide showed better inhibitory activity with IC<sub>50</sub> Value of 0.095±0.27 µM and Steady-state ATPase results revealed that some compounds exhibited promising inhibitory activity (IC<sub>50</sub> values of 2.408±0.46 to 2.720±0.69, 2.676±0.53 µM ). A molecular docking study was performed to evaluate interaction into the binding site of kinesin spindle protein; this interaction influencing may support Eg5 inhibitory activity. Some of the compounds in present analogs could be a promising lead for advanced Eg5 inhibitory agents’ discovery.</p> <p><img src="blob:" /></p> <p>Fig. Design of Eg5 Inhibitors</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #156 Pharmacognostical and phytochemical screening on leaves of Ipomoea sagittifolia Burm. F 2022-03-29T13:40:17+00:00 Muthulakshmi R <p>The drug evaluation and bioassay of traditional herbs of various herbal systems are now getting more momentum throughout the world. The present study provides information in respect of their identification, standardization of herbal drugs of the folk medicinal practice of present, and enrichment of Ayurvedic Pharmacopoeia. It is high time now to evaluate scientifically the information stored in different herbal medicine systems of the world in terms of their pharmacognostic and phytochemical characterization. So knowledge of the pharmacognosy of individual medicinal plants is a very important aspect for herbal based drug discovery. Therefore in this study, an attempt has been made to evaluate such ethnomedicinally important plant, pharmacognostical and phytochemical analyses which are still unexplored. In this study, different pharmacognostical parameters of <em>Ipomoea sagittifolia</em> Burm.f. belonging to the family of Convolvulaceae, an ethnobotanically important medicinal plant, has been investigated. WHO recommended physico-chemical determinations and authentic phytochemical procedures. The physicochemical, morphological, and histological parameters presented in this paper may be proposed as parameters to establish the authenticity of the leaf of <em>I. sagittifolia</em> and may possibly help to differentiate the drug from its other species. In the leaf extract, the detected phytochemical groups are alkaloids, flavonoids, steroids, and triterpenoids, reducing sugars, tannins, gums, and saponins, etc. This study will be beneficial to herbalists and pharmacognostical and phytochemical for proper evaluation and validation of folk drugs. Herbal drugs used in various traditional medicine need detailed investigation with an ethnopharmacological approach.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #157 Simultaneous detection of biogenic amines metabolites (homovanillic acid and vanillyl mandelic acid) in urine sample of rodents by HPLC-UV method 2022-03-29T13:44:34+00:00 Vrushali Bhalchim Sunil Shewale Vaishali Undale <p>A simple, effective, and sensitive HPLC with UV detector was developed for detection of these biogenic amines metabolites in the urine sample of rodents as biotargets for neurological diseases like Parkinson’s disease, Alzheimer’s disease, Depression. The method includes the mobile phase combination of acetonitrile (ACN) and o-phosphoric acid (pH 2) in a ratio of (30:70 v/v), pH 2.2; the spectroscopic conditions were maintained for separation of analytes Kromosil C8 column 5 µm (125 X 4.6 mm) column at an ambient temperature of 25° C, at a flow rate 0.5 mL/min using EZ Chrome elite, Agilent HPLC system. Different mobile phases were used on a trial and error basis for the separation of these two metabolites. Validation of the developed method was carried out according to ICH guidelines. The calibration curve was linear over the concentration range of 10–35 μg/mL with regression coefficient (r<sup>2</sup>) 0.998 for HVA and 0.996 for VMA for both metabolite components. The limit of quantitation (LOQ) was 1 ng/mL, and the limit of detection (LOD) was 1 ng/mL. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid and vanillyl mandelic acid in urine samples.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #158 A stability indicating RP-UPLC method for the simultaneous estimation of Metformin, Dapagliflozin and Saxagliptin in bulk and tablet dosage form 2022-03-29T13:49:55+00:00 Devi Velmurugan Kamalakannan Dhanabalan Kamalathiyagarajan D Sekar Vairavel Sambathkurmar Ramanathan <p>To develop a simple, accurate, precise, and rapid analytical method validation for stability-indicating RP-UPLC method for the simultaneous estimation of Metformin, Dapagliflozin, and Saxagliptin in bulk and tablet dosage form. The separation was carried out on CHS C18 (100 x 2.1 mm) 1.7 µm column, with the mobile phase composition of Water: Methanol (50:50 v/v). Flow rate: 0.3 mL/min. UV detection was carried out at 222 nm. The developed method was validated for linearity, accuracy, precision, the limit of detection, and quantification as per ICH guidelines. The linearity of the drugs from the concentration range of 5-30 µg/mL was established by constructing the calibration curve with a concentration on the X-axis and peak area on the Y-axis with the correlation coefficient of 0.999. The retention time of Metformin, Dapagliflozin, and Saxagliptin was found to be 1.060 min, 1.502 min, and 2.176 min. The %RSD of system precision for Metformin, Dapagliflozin, and Saxagliptin was found to be 1.0, 0.7, and 0.7, respectively. The %RSD of method precision for Metformin, Dapagliflozin, and Saxagliptin was found to be 0.7, 0.7, and 0.8, respectively. Percentage recovery was obtained as 99.63%, 100.26%, and 99.78% for Metformin, Dapagliflozin, and Saxagliptin, respectively. A new simple analytical method has been developed for the Simultaneous Estimation Of Metformin, Dapagliflozin and Saxagliptin in Bulk and Tablet Dosage Form.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #160 Study on wound healing activity of papain plant enzyme incorporated in chitosan hydrogel 2022-03-29T13:56:07+00:00 Chetna Waghale <p>Papain enzyme possesses wound healing, anti-inflammatory, and anti-fungal activity. Chitosan has topical wound healing activity, and its activity would be improved when combined with papain enzyme. In the presented study, the chitosan hydrogel containing papain was prepared and applied to wounded skin to check its anti-inflammatory activity. The hydrogel was prepared using chitosan in variable concentrations (1-5%), and papain (0.5%) was added. Glacial acetic acid was used to solubilize the chitosan. The topical gel was evaluated for appearance/clarity, pH, viscosity, spreadability, bio adhesive strength, and tube extrudability. Batch CP8 containing 5% chitosan and 0.5% papain showed the highest spreadability, adhesive strength, and extrudability and hence was selected for in vivo study. A wound healing study was carried out on albino mice by creating wounds by excision, incision, and burn. The treatment of mice was started by applying topical gel till the wound healed. The progressive changes in wound area were measured in mm<sup>2</sup> by tracing wound boundaries on transparent paper at every 4-day interval. It was observed that when the concentration of polymer was increased, spreadability and adhesive strength were increased. Prepared hydrogels showed pseudoplastic behavior during viscosity determination using Brookfield viscometer. Amongst all the studied formulations, batch CP8 showed good gelling ability, pH in range, excellent spreadability, good adhesive strength, extrudability and was stable at temperatures 5±3 °C and 25±3 °C during three months stability study. After applying the gel over the wound at the end of 16 days of study, it was observed that batch CP8 healed 99.77% wound, which was higher as compared to a positive control (standard drug- salicylic acid), which covered 98.8% of the wound, Plain Gel covered 87.10% wound, and negative control (without gel) covered 84.70% wound. From the experimental evidence of in-vitro studies, it was observed that papain enzyme is a promising alternative to conventional drug therapy; it showed significant wound healing activity. The developed herbal formulation was stable, safe, and effective over synthetic formulations for the treatment of wound healing activity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #161 A validated stability-indicating UPLC method development and forced degradation study for simultaneous quantification of ibuprofen and caffeine in capsule dosage form 2022-03-30T14:22:18+00:00 Carolinnimila Innacy Devi Velmurugan Sambathkumar Ramanathan <p>A rapid and stability-indicating Ultra-Performance Liquid Chromatography (UPLC) method was developed for simultaneous quantification of Ibuprofen and Caffeine in their combined dosage form, especially to get some more advantages over other methods already developed for this combination using Photo Diode Array (PDA) detector. The separation was achieved on a UHP ASB C18 column (2.1 mm X 50 mm, 1.9 µm) at a wavelength of 254 nm, using a mobile phase A: Mobile B (Methanol: Buffer) (70:30 v/v) in an isocratic elution mode at a flow rate of 0.1 mL/min. The retention time for Ibuprofen and Caffeine was found to be 6.5 min and 1.9 min, respectively. The percentage RSD of the Ibuprofen and Caffeine were and found to be 0.6 and 0.5, respectively, and the percentage recovery was obtained at 100.3% and 100.6%. The method showed excellent linear response with correlation coefficient (R<sup>2</sup>) values of 0.999 for both drugs. Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (% RSD) ≤ 2.0. The drug was subjected to acidic, alkaline media, boiling, heat, humidity, and oxidizing agent to apply stress conditions. The developed method did not show any interference of degrading peaks generated under forced degradation studies. The developed method was found to be simple, accurate, precise, and cost-effective. The forced degradation studies indicated that the degradants and excipients are within the limit. Hence, the developed method was suitable for quantitative analysis of Ibuprofen and Caffeine both in bulk and combined pharmaceutical dosage form. The study suggests that the developed UPLC method can be used for the assessment of drug purity and stability.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #164 A Stability-indicating UPLC-TUV method for the simultaneous estimation of Netarsudil and Latanoprost in bulk drug and ophthalmic preparations 2022-03-30T14:26:40+00:00 Karthick Saravanan Kamalakannan Dhanabalan Mohammed Eashak M Gowtham Kumar Siva Shanmugam Sambathkurmar Ramanathan <p>The aim here was to develop a specific, precise, accurate, linear, simple, rapid, validated, and cost-effective stability indicating UPLC-TUV method for the simultaneous estimation of Netarsudil and Latanoprost in bulk drug and ophthalmic preparations. The estimation was carried out on CHS C18 (2.6 x 50 mm, 1.6 µm) column, with the mobile phase composition of 60% 0.1N KH<sub>2</sub>PO<sub>4</sub>: 40% methanol. Flow rate: 0.3 mL/min. UV detection was carried out at 210 nm. The developed method was validated for linearity, accuracy, precision, the limit of detection, and quantification as per ICH guidelines. The linearity of the drugs from the concentration range of 5-30 µg/mL was established by constructing the calibration curve with a concentration on the X-axis and peak area on the Y-axis with the correlation coefficient of 0.999. The percentage recovery of drugs was found recovered within the range of 98.93-101.26%, and the mean of %recovered within the range of 99.93 -100.90%. Netarsudil and Latanoprost were eluted at 1.153 min and 1.480 min, respectively, with good resolution. Plate count and tailing factor were very satisfactory, so this method was optimized and to be validated. A new simple analytical method has been developed for the stability-indicating UPLC-TUV Method for the simultaneous estimation of Netarsudil and Latanoprost in bulk drug and ophthalmic preparations.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #165 Design and synthesis of allosteric fourth-generation EGFR tyrosine kinase triple mutant selective inhibitors for the treatment of non-small cell lung cancer 2022-03-30T14:51:10+00:00 Ansari Azim Zakir Mohd Usman Mohd Siddique <p>Non-small cell lung cancer (NSCLC) is the leading cause of mortality in oncology, and EGFR-TK plays a critical role in this disease. As a result, EGFR-TK is a viable target for therapeutic development in NSCLC. The T790M EGFR TK mutation was resistant to both first-generation and second-generation (selectivity issue) EGFR TK inhibitors. Although third-generation drugs (Osimertinib) can overcome the EGFR T790M mutation, a recent C797S mutation makes these agents ineffective against it. All of the currently available EGFR kinase inhibitors target the kinase’s highly conserved ATP-site, underlining the need for therapeutics with a different mechanism of action (allosteric binding). EAI001, EAI045, JBJ-04-125-02, DDC4002, and a series of small compounds (fourth generation) having an affinity for the EGFR allosteric site have been discovered and are currently being investigated. To overcome EGFR T790M/C797S resistance, allosteric mutant-selective fourth-generation EGFR inhibitors look to be a promising treatment approach. We present the discovery, development, and structural characterization of allosteric mutant selective EGFR inhibitors based on an anilino pyrimidine scaffold. Our structure-based medicinal chemistry effort resulted in an inhibitor (3) of the EGFR (L858R/T790M) and EGFR (L858R/T790M/C797S) mutants with an IC<sub>50</sub> of 10 nM and good selectivity, as shown by kinome profiling. Further research into allosteric anilinopyrimidine inhibitors might pave the way for new treatment alternatives for targeting drug-resistant EGFR mutations.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #167 Development of a polyherbal formulation in the management of osteoporosis in post menopausal women 2022-03-30T15:03:40+00:00 Shri Vijaya Kirubha T Senthamarai R Balasubramanian P Kavitha V <p>Osteoporosis affects all women, and osteoporotic fractures are more common in menopausal women, which accounts for significant morbidity and mortality. Certain herbs have potential effects in promoting gonadal function, fracture healing and are suitable to counteract/ prevent postmenopausal osteoporosis as compared to synthetic drugs that have been reported for their side effects, including hypercalcemia, vaginal bleeding, risk of endometrial and breast cancer. In the current research, the herbal drugs that have been claimed to improve bone mineral density, lower menopause symptoms, and recommended as an herbal tonic for osteoporosis in women were selected and formulated as capsules. The poly herbal formulation (PHF) containing the alcoholic extracts of Meremmiaumbellata (Convulvulaceae), Hydrocotylejavanica (Apiaceae), and Peristrophebicalyculata (Acanthaceae) was developed and screened for anti-osteoporosis activity in experimental rat models. Results obtained in the present study indicated that treatment with PHF (500 mg/kg) showed a significant increase in femur length, femur diameter, restoration of serum calcium and alkaline phosphate levels, improvement in body weight as compared to positive control rats. Femur bone weight and density were significantly restored with improvement in bone breaking strength after the treatment of PHF. Histopathological study of the femur bone further supported the antiosteoporotic activity. These results showed that developed Poly Herbal Formulation showed significant protection against ovariectomy-induced osteoporosis in rats. Our present investigation supports the use of the developed polyherbal formulation in the treatment of osteoporosis, especially in post menopausal women.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #168 An in silico approach to identify potential medicinal componds for anti-rheumatoid arthritis activity using polyherbal transdermal patch 2022-03-30T15:08:01+00:00 Tamilselvi L Senthamarai R Shri Vijaya Kirubha T <p>Herbal transdermal patches can develop valuable assessment and drug safety by additional site-specific the way and temporal position in the body’s imperative to reduce the number and size of doses required to achieve the objective of systemic medication during topical application to the intact skin surface. Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease of unknown cause. It is characterized by persistent inflammation that primarily affects the peripheral joints. Various treatments and management have been in progress on wide ranges. Molecular docking is a virtual screening method that cutback the expenses and time duration for the identification of pharmacophores from natural products. Polyherbal transdermal patch was developed by using ethanolic extracts of leaves of <em>Cardiospermum halicacabum</em> and rhizomes of <em>Drynaria quercifolia</em>. The developed polyherbal transdermal patch was subjected to Gas Chromatography-Mass Spectroscopy (GC-MS) for Identification of phytoconstituents. This in-silico study has been screen the phytochemical components binding with human Interleukin- 6 (IL-6) receptor by using AutoDock Vina software. The results obtained after docking showed a good binding affinity and implicated that the active phytoconstituents of the developed formulation would be a supportive measure for the treatment of Rheumatoid Arthritis</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #170 Formulation and evaluation of temperature-sensitive doxycycline in-situ gelling system for the treatment of periodontitis 2022-03-30T15:12:09+00:00 Mangesh Godbole <p>About 70% of the population suffers from dental problems. Oral antimicrobial agents are used to treat the infections occurred in the periodontal cavity. The objective of the presented study was to reduce the frequency of Doxycycline administration and to prolong the duration of action for better patient compliance in periodontitis by formulating a temperature-sensitive oral in situ gelling system of Doxycycline. Doxycycline in-situ gel was formulated using different concentrations of Poloxamer-407 (16, 17, 18% w/v) alone or in combination with different concentrations of bioadhesive polymer viz, pectin, HPMC K100, sodium alginate (0.5, 1, 1.5 w/v) by cold method. Preliminary screening without drugs was carried out to select the stable formulation. Batches having a clear and transparent appearance and stable were selected for further study, and doxycycline 0.02% w/v was added. Formulated batches were evaluated for gelation time, gelation temperature, pH, viscosity, spreadability, mucoadhesive strength, and in-vitro drug release. Formulation PS9 (Poloxamer 407 18 % w/v and sodium alginate 1.5% w/v) showed excellent gelling ability, gelation occurred in 30 sec at 34° C, drug content was 96.91±0.61%, 96.4±0.33% drug was released at the end of 8 h. Formulated gel exhibited excellent bioadhesive strength and spreadability. Antibacterial activity of formulation PS9 against a three-day observation period was concluded as excellent. It retained most of the physical as well as functional characteristics even after exposure to extreme conditions for 90 days. The local delivery of antibacterials will enhance patient compliance in the treatment of periodontitis. It involves the direct application of antibacterials into diseased subgingival sites, which helps avoid limitations related to the oral route. Such local delivery also offers controlled release of drug for a longer duration, so a single dose is effective to maintain therapeutic concentration within the gingival crevicular fluid for a longer period.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #171 HPTLC method development for simultaneous estimation of Andrographolide, Gallic acid and Quercetin from herbal extracts with implementation of Quality by Design (QbD) 2022-04-05T09:11:24+00:00 Monika Jadhav Pratima Tatke <p>Development of Quality by Design (QbD) based sensitive, economic and robust high performance thin layer chromatographic (HPTLC) method for simultaneous estimation of Andrographolide (A), Gallic acid (G) and Quercetin (Q) in herbal extracts. The chromatographic separation was carried on Merck TLC aluminum sheets of silica gel 60 F254 (20 × 10 cm) with a mobile phase of toluene: ethyl acetate: methanol: formic acid (4:3:1:0.05) with densitometric scanning at 232 and 256 nm. QbD approach was implemented by investigating Critical Method Parameters (CMPs) through regular two-level factorial design by using a trial version of Design Expert-13 software and evaluated for their effect on selected critical analytical attributes that are retention factor (R<sub>f</sub>) and peak area. The Pareto charts, 3D response surface plots, and contour plots (Figure 1) for the constructed model demonstrated a significant influence of the selected factors on responses of A, G, and Q. The results obtained using the regular two-level factorial design for screening of CMPs indicated that the composition of the mobile phase ratio had a significant effect on the retention factors and areas of A, G, and Q. The method parameter of saturation time and wavelength had a minor effect on the R<sub>f</sub> values, while the wavelength had a significant effect on all areas. Under the optimized conditions, the biomarkers were suitably resolved with R<sub>f</sub> values of 0.38±0.02, 0.24±0.02, and 0.50±0.02 for A, G, and Q, respectively, with the linearity in the concentration range of 400- 2400 ng/band for A, 200-1200 ng/band for G and Q, high accuracy of 98.9-99.8%, and intra- and interday precision of %RSD &lt;2%. This validated HPTLC method developed through a QbD approach was successfully employed for quantification of A, G, and Q in selected herbal extracts. The optimized method was proved to be economical, robust, time-saving and thus, can be used for simultaneous estimation of A, G, and Q in other herbal extracts and herbal formulations.</p> <p><img src="blob:" /></p> <p>Fig. Contour plots of Critical Analytical Attributes (CAA)</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #172 A novel instrumental method for simultaneous estimation of cardiovascular drugs 2022-04-05T09:15:29+00:00 Celina Nazareth Pooja Shelar <p>The market is flooded with a combination of drugs in various dosage forms. Multi-component formulations are in demand due to greater patient acceptability, increased potency, multiple actions, fewer side effects, and quicker relief. Analytical methods are needed to analyze multi-component formulations. Among the instrumental method for analysis, there is a renewed interest in UV Spectrophotometric methods due to methods being rapid, simple, and cost-effective compared to sophisticated HPLC, LC-MS/MS methods. Cardiovascular disease continues to occur in epidemic proportions globally. Hence multiple strategies are needed for control and reversal so as to reduce mortality and morbidity. A review of available literature indicated that ample analytical methods are available for the estimation of Metoprolol and Atorvastatin. These include HPTLC, Reverse phase HPLC methods for the drugs either individually or combined with other drugs. However, there is no reported UV-spectroscopic method for simultaneous estimation of the drugs based on the absorption correction principle. Hence, there is a need for a simple UV-spectroscopic method for the simultaneous analysis of cardiovascular drugs. A novel UV-spectroscopic method has been developed for the simultaneous estimation of cardiovascular drugs by the absorbance correction method. Methanol was used as a solvent, and water was used as a diluent for the analysis. The choice of wavelengths was based on the absorption correction principle. Accordingly, one wavelength was chosen where both drugs absorb, while the second wavelength was chosen such that only one drug was absorbed. The developed method was validated as per ICH guidelines. Linearity was obtained in the range of 10–100 µg/mL and 2–100 µg/mL for metoprolol tartrate and Atorvastatin calcium, respectively. The method was found to be accurate, precise, sensitive, and robust. The percentage assay value was found to be 99.10% for Metoprolol tartrate and 98.18% for Atorvastatin calcium which was within the acceptance criteria (90–110%). Hence, the developed UV method is a valuable, cost-effective tool for the quality control of drugs in analysis.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #173 Pharmacological evaluation of PR/HC/1718/004 formulation for anti-stress activity in chronic unpredicted mild stress (CUMS) in mice 2022-04-05T09:18:17+00:00 Priyanka Mahadik Vaishali Undale Pooja Bhalerao <p>Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. It is the second leading cause of morbidity and also leads to suicide. Depression has a cluster of distinguishable symptoms, including psychological, behavioral, and physical changes that are seen due to alterations in monoamines, i.e., norepinephrine and serotonin levels in the brain and excessive cortisol secretion. Literature survey shows that polyherbal formulation containing herbs such as <em>Withania somnifera</em>, <em>Convolvulus pluricaulis</em>, <em>Nardostachys jatamansi</em>, <em>Valeriana wallichii</em>, <em>Myristica fragrans</em>, <em>Ziziphus mauritania</em> and <em>Crocus sativus</em> possess antidepressant, antioxidative activity, antianxiety activity, hypnotic activity (Sleep). The present study was designed to investigate the antidepressant potential of this combination of these herbs as a polyherbal formulation in chronic unpredictable mild stress. Chronic exposure to different stress over a period of 6 weeks leads to a decrease in monoamines neurotransmitters levels, serotonin, norepinephrine, and dopamine level. Oxidative dysfunction (increased lipid peroxidation, nitrite level decreased activity of superoxide dismutase, catalase, and reduced glutathione level), increased plasma corticosterone level and MAO-A level, increased immobility, memory impairment as compared to the normal group. The treatment with marketed formulation for six weeks significantly improved behavior alteration, oxidative damage, antioxidant enzyme activity, decreased corticosterone, MAO-A enzyme as compared to CUMS group and showed equivalent effect with other herbal standards. The present study result suggests that the marketed polyherbal formulation was able to reduce the stress-induced depressive symptoms in mice and could provide a rationale for their therapeutic management for major depression.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #175 Anti-obesity activity of Annona squamosa (Linn.) leaves extract on monosodium glutamate - High fat diet-induced obese mice model 2022-04-05T09:30:13+00:00 Ravi Pratap Singh Ashok Kumar Patnaik <p>The Methanolic extract of leaves of <em>Annona squamosa</em> (Linn.) has been tested for their anti-obesity property. The extracts were examined for the presence of phytoconstituents, antioxidant activity, digestive enzyme activity, hypoglycaemic effect, hypophagic effect &amp; histology of adipose tissue, and fatty liver changes by using MSG-HFD induced obesity in Swiss albino mice. Animals treated with ASPE have reduced the increase in body weight, periepididymal fat weight, etc. The anti-obesity activity produced by ASPE may be because of inhibition of amylase enzyme, antioxidant activity, the presence of tannins, and flavonoid content. These findings suggest that the anti-obesity actions of ASPE may be partly mediated by delaying the intestinal absorption of dietary fat. The plants have shown the presence of essential phytoconstituents like sitosterols and stigmasterols in NMR, TLC, and HPTLC study whereas some common constituents like saponin, flavonoids, steroids, triterpenoids, glycosides, and anthocyanin were also present in the preliminary phytochemical study. In this study, ASPE is found to be beneficial for the suppression of obesity and some associated complications.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #177 Microwave-assisted synthesis of surface passivated fluorescent carbon nanodots from Buchnanialanzan leaves extract 2022-04-05T09:33:06+00:00 Pradip Jana Abhimanyu Dev <p>The current work is designed to synthesize fluorescent carbon nanodots (CDs) by microwave treatment of <em>Buchnania lanzan</em> leaves extract. The methanolic extract of <em>Buchnania lanzan</em> leaves serves as the carbon precursor for CDs synthesis. Leaves extract was initially treated in a microwave oven, and the residue obtained was cooled at room temperature, and then it was reconstituted with polyethylene glycol 4000 (PEG 4000) solution. The obtained solution was again treated in a microwave oven, and the residue was cooled and reconstituted with Milli-Q. Here, PEG 4000 acts as a surface passivating agent. Afterward, the brown-colored passivated CDs (CDPs) solution was centrifuged, and the supernatant was filtered through a syringe filter to remove dark carbonaceous matters and to get pure CDPs. Finally, CDPs solution was lyophilized in order to obtain CDPs in powder form. The synthesized CDPs were studied by several characterization techniques like- UV-visible spectroscopy, Fluorescence spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and zeta potential. The as-prepared CDPs solution was of brown color in daylight while it exhibited green fluorescence under UV light. The UV-visible spectrum of CDPs showed a sharp peak at 282.50 nm and a shoulder peak at about 350 nm, which is in accordance with earlier reports. CDPs exhibited an excitation-dependent emission behavior in the fluorescence spectrum, which is a distinct characteristic of CDs. FTIR spectrum of CDPs suggested the presence of carboxyl, amino surface functional groups, and aromatic C=C bonds. Further, the negative zeta potential of -9.77 mV supports the FTIR data, indicating CDPs surface rich in carboxyl functionality. As in this study, a simple and cost-effective synthesis of fluorescent CDPs from a renewable and abundant plant source is carried out; this method could offer a large-scale synthesis of carbon nanodots for the applications in the fields of drug delivery bioimaging, photocatalysts, biosensors, etc.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #178 Evaluation of RV forte capsules and TCCT (curcumin based formulation) tablets for its activity against anti-TB drug induced hepatotoxicity in wistar rats 2022-04-05T09:35:58+00:00 Snehal Bodare Vaishali Undale <p>Anti-tubercular drugs (ATD) are the leading cause of drug-induced acute liver failure in India. The most effective first-line antitubercular drugs (ATD), Isoniazid (INH), and Rifampicin (RIF) have been used to treat tuberculosis (TB). The majority of potent ATDs, including INH, RIF, and Pyrazinamide, are hepatotoxic. When these medications are used together, the risk of hepatotoxicity increases, both of these medications are considered to be hepatotoxic due to their high potency against the tuberculous bacillus. The combination of both these drugs, however, resulted in the increase of hepatotoxicity both in adults and children. Anti-TB drugs are one of the commonest groups underlying idiosyncratic hepatotoxicity worldwide. The co-administration of hepatoprotective herb with the AntiTB drug may reduce the induced hepatotoxicity. The aim of the present study was to explore the hepatoprotective effect of RV forte capsules (resveratrol-based formulation) and TCCT (curcumin-based formulation) tablets for their hepatoprotective potential against INH induced hepatoxicity in Wistar rats at the dose of 100, 200, and 400 mg/kg dose. In this research work, RV forte TCCT tablets at 400 mg/kg dose showed a significant hepatoprotective effect against INH-induced hepatotoxicity, probably by reducing the oxidative stress as they exhibited a reduction in AST, ALT, and oxidative parameters, SOD, CAT, MDA. The liver histopathology also showed the amelioration of INH-induced hepatotoxicity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #181 Role of natural phytoconstituent drug development against Nipah virus 2022-04-05T09:56:46+00:00 Shubham Srivastava <p>The Nipah virus, a paramyxovirus with Pteropus bats as its animal reservoir, was initially detected in a significant outbreak of severe encephalitis in Malaysia in 1998 among people who came into contact with ill pigs. Humans are already sensitive to the Nipah virus; many strains are capable of limited person-to-person transmission, and, as an RNA virus, it has an extraordinarily high rate of mutation. With the huge concern of the Nipah virus becoming another pandemic, and synthetic drugs are still incompatible and have major side effects, the emphasis on drug development using natural phytoconstituent’s can be a major boost to the healthcare system. In this abstract, the two phytoconstituent’s that are hydroxychavicol extracted from <em>Piper beetle</em> and mangiferin from mango was docked against the Nipah virus protein via AutoDock software as mentioned in the protein data bank, and it is observed that it shows good binding energy result and hence they can suggest that combined effect of both these phytoconstituent’s can be used for the treatment against Nipah virus. Hence it can be concluded that in the future, these phytoconstituents can be used as safe treatment options. However, further clinical evaluations are needed for more studies.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #183 Development of polymeric nanoparticles of Forskolin and Rutin: Optimisation and in-vitro characterization 2022-04-05T09:59:21+00:00 Pallavi Dahiya Ameeduzaffar Zaffar <p>The aim here is to optimize and characterize the chitosan-coated nanoparticles of Forskolin and Rutin for ocular delivery for the treatment of glaucoma. Forskolin and Rutin nanoparticles coated with chitosan were prepared by the emulsion solvent evaporation method. A four-factor three-level Box-Behneken design was used to investigate the influence of independent variables on particle size and entrapment efficiency. Characterization was done for particle size, entrapment efficiency, and in-vitro drug release. The optimized nanoparticles showed particle size and entrapment efficiency of 135 nm and 74.09%, respectively. The in-vitro release study of both drugs (Forskolin and Rutin) showed a sustained release up to 24 h. Chitosan-coated nanoparticles of Forskolin and Rutin were successfully developed and optimized by Box-Bhekhen statistical design using chitosan, PLGA, and PVA as an independent variable. Nanoparticles were found to be spherical in shape 200 nm with positive zeta potential. The in-vitro release study shows a longer duration. In future, an in-vivo study will be performed to obtain the pharmacokinetic and pharmacodynamic study of the nanoparticles.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #184 Anticonvulsant activities of the leaves of canavaliagladiata(Jacq.) DC. Using zebra fish 2022-04-05T10:02:51+00:00 Velmani C Shri Vijaya Kirubha T Senthamarai R <p>Epilepsy is one of the most common serious neurological disorders, responsible for substantial morbidity and mortality due to the limited efficacy and negative properties of antiepileptic drugs. Epilepsy treatment is based on the use of drugs that aim to inhibit repetitive neuronal discharges, and consequently, the recurrence of seizures. However, despite the large number of antiepileptic drugs currently available, about 30-40% of patients with epilepsy do not respond satisfactorily to treatments. Therefore, the investigation of new therapeutic alternatives for epilepsy becomes relevant, especially the search for new compounds with anticonvulsant properties. The therapeutic potential of plant-derived bioactive compounds has been a target for alternative treatments for epilepsy. Medicinal plants used for the treatment of epilepsy are potentially a valuable source of novel antiepileptic small molecules. To identify anticonvulsant secondary metabolites, we performed an in-vivo, zebrafish-based screen of medicinal plants used in Southeast Asia for the treatment of seizures. <em>Canavalia gladiata</em> (Jacq.) Dc belonging to the family Papilionaceae was identified as having significant anticonvulsant activity in zebrafish with seizures induced by the pentylenetetrazol (PTZ). The use of animal models for drug screening, such as zebrafish, contributes to a better understanding of the mechanisms involved in seizures and for investigating methods and alternative treatments to decrease seizure incidence. The sensitivity of zebrafish to chemoconvulsants and its use in genetic approaches reinforces the contribution of this animal to epilepsy research. Moreover, we summarize advances in zebrafish-based studies that focus on plant-derived bioactive compounds with potential antiseizure properties, contributing to the screening of new drugs for epilepsy treatment.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #186 Design, synthesis and evaluation of dual MAO/AChE inhibitory capabilities of some novel substituted aryl hydrazones 2022-04-05T10:05:54+00:00 Sandeep Kumar Harish Jagannadhula Senthil Raja Ayyannan <p>Monoamine oxidase A and B (MAO-A/B) are FAD-containing enzymes found in the outer mitochondrial membrane and are responsible for the oxidative deamination of biogenic monoamines. The tissue distribution of MAO-B is more (80%) in the brain. The high concentration of MAO-B in the brain decreases dopamine level and increase oxidative stress. On the other hand, acetylcholinesterase (AChE) catalyzes the hydrolysis of acetylcholine (ACh) into acetate ions and choline in neuronal synapses. The high activity of AChE causes depletion of acetylcholine levels in the brain and periphery, which leads to impaired learning and memory deficit. Recently we have identified a piperonylic acid-derived hydrazone (Fig. 1) as a potent dual MAO/AChE inhibitor. In order to investigate the role of benzodioxole moiety in the lead inhibitor (SBH-3) on the enzyme activity, we designed a series of open chain (01-07) and simple (08-16) aryl hydrazones using the ligand-guided design and optimization strategy. The synthesis of designed molecules was accomplished by multistep synthesis starting from dimethoxy benzoic acid (compounds 01-07) and 4-chlorophenylacetic acid (compounds 08-16). All synthesized hydrazones were characterized by using IR, NMR, and Mass spectral techniques, and their dual enzyme inhibitory potential was evaluated against MAO-B and AChE using colorimetry assay and Ellman’s method, respectively. A set of 16 compounds was designed, synthesized, and evaluated against MAO-B and AChE. The tested compounds showed nanomolar to micromolar inhibitory potential with IC$_{50}$ values between 7.009±0.012 µM (Compound 03) between 16.998±0.023 µM (Compound 04) against MAO-B, whereas for AChE, the IC$_{50}$ values ranged from 0.024±0.007 µM (Compound 03) to 69.096±0.54 µM (Compound 11). The open-chain analog, compound 03, emerged as a lead AChE inhibitor with an IC$_{50}$ value of 0.052±0.006 µM. Thus, the lead optimization study yielded a selective AChE inhibitor (compound 03) that is two times more potent than the earlier dual inhibitor SBH-3. Based on the results, it can be concluded that the presence of a bulky hydrophobic benzodioxole moiety at the amido terminal highly influences the selective and dual AChE/MAO-B inhibition potential of aryl hydrazones.</p> <p><img src="blob:" /></p> <p>Fig. Ligand-based design strategy and the structure of the lead compound</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #187 Green synthesis of silver nanoparticles from leaves of Clerodendrum glandulosum Lindl. and evaluation of its antimicrobial and antioxidant activities 2022-04-05T10:09:58+00:00 Garima Agrawal Biswatrish Sarkar Rajdeep Saha <p>Nanotechnology has been recognized as one of the sprouting inter-disciplinary research fields. Silver nanoparticle (AgNP) has gained increased attention due to their unique properties and multifaceted applications. The development of resistance of bacteria to antibiotics is becoming an area of concern which has led to renewed interests in investigating the potency of AgNP. Green chemistry utilizes the plant material for the synthesis of nanoparticles, mitigates the complications associated with physical and chemical methods of synthesis of the same. This study was aimed to fabricate green synthesized silver nanoparticles (AgNP) using leaves of <em>Clerodendrum glandulosum</em> Lindl. as a reducing and stabilizing agent. Further, its antimicrobial and antioxidant activity was evaluated. 1 mM of silver nitrate solution in 240 mL of Millipore water was prepared, and 8 mL of plant extract was added to it. The pH of the reaction mixture was adjusted to 10. It was then placed on a magnetic stirrer at 700 rpm for 30 min. Color change from pale yellow to dark-brown was observed, which indicated the formation of the nanoparticle. The synthesized nanoparticle was centrifuged and washed three times, and the nanoparticle was collected. The preliminary characterization was done by UV-visible spectroscopy. The synthesized nanoparticle was also characterized by Dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared (FTIR), and Field-emission scanning electron microscopy (FESEM). The antimicrobial activity was performed against Gram-positive and Gram-negative bacteria (<em>S. aureus</em> and <em>E. coli</em>), respectively. DPPH &amp; ABTS assay was performed for evaluation of the antioxidant activity. The SPR region of 460 nm was obtained, and other characterizations were done, which confirmed the formation of <em>Clerodendrumglan dulosum</em> Lindl. reduced Silver nanoparticle (CgAgNP). Zone of inhibition, MIC &amp; MBC was observed against <em>S. aureus</em> and <em>E. coli</em>. The synthesized nanoparticle exhibited excellent antibacterial and antioxidant activity. Hereby a novel approach for green synthesis of AgNP by utilizing <em>C. glandulosum</em> Lindl. is reported. Green synthesis is environment-friendly, economical, and a viable substitute for chemical and physical procedures. Plant-based silver nanoparticle shows excellent biological activities so, it can be utilized for various therapeutic actions and site-targeted treatments.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #188 Evaluation of herbal composite for its activity against anticancer drug induced hepatotoxicity in Wistar rats 2022-04-05T10:14:15+00:00 Nishant Mante Vaishali Undale <p>The liver plays a crucial role in the metabolic elimination of most drugs and other foreign compounds, thus making it an important target for toxicity. The hepatotoxic response is expressed in the characteristic form of cell death in specific zones of acinar regions in the liver. Keeping the above perspectives in mind, the herb, RV forte (resveratrol-based formulation) capsules, and TCCT (curcumin-based formulation) tablets traditionally used in the treatment of hepatotoxicity were selected, there is a need to explore the full potential of this combination as a hepatoprotective agent. The herbal composite consists of a combination of RV forte (resveratrol-based formulation) and TCCT (curcumin-based formulation) tablets. All the herbs used in the composite are proven to be safe and clinically used in many herbal formulations. The herbal composite is a unique combination of selected herbs and is proposed to be effective in minimizing the toxicities of anticancer therapy. In this study we found that in RV forte (resveratrol-based formulation) (C100 and C400): treated groups C400 dose showed more significant hepatoprotection as compared to C100 and in Resveratrol (R100 and R400) treated groups R400 dose showed more significant hepatoprotection as compared to R100. The RV forte (resveratrol-based formulation) at a dose of 400 mg/kg body weight showed more significant hepatoprotection against CTX induced hepatotoxicity as compared to all other treatment groups C100, R100, R400.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #189 Analytical method development and validation for the estimation of Tolterodine in bulk and dosage form 2022-04-05T10:19:54+00:00 Mrunali Patil <p>A new simple, accurate, and economical reverse-phase high-performance liquid chromatographic method was developed for the estimation of Tolterodine in bulk and tablet dosage form. The separation was eluted on Agilent TC C18 column (250 mm x 4.6 mm; 5 μm) using a mobile phase mixture of 0.1% orthophosphoric acid and methanol in a ratio of 50:50 v/v at a flow rate of 1.2 mL/min. The detection was made at 220 nm. The retention time was 3.7 min. The calibration curve was linear over the 5-30 μg/mL concentration range. The percentage recovery obtained was 100.36%. The proposed method was validated as per the ICH guidelines parameters like linearity, specificity, precision, accuracy, robustness, and ruggedness. The method was accurate, precise, specific, and rapidly found to be suitable for the quantitative analysis of the drug and dosage form.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #191 Evaluation of herbal extract(HC) for its activity against anticancer drug-induced bone marrow toxicity in Wistar rats 2022-04-07T14:12:32+00:00 Vishwajit Burse Vaishali Undale <p>Among all side effects seen, those associated with the effects of anticancer therapy on the bone marrow (BM) represent a potentially dangerous and even life-threatening circumstance. Because most anticancer treatments affect rapidly dividing cells preferentially, BM is an ideal target for these effects. This is the primary reason that myelosuppression is among the complications most frequently seen. Bone marrow is a complex organ responsible for the regulation of hematopoietic cell distribution throughout the human body. Myelosuppression is a common and anticipated adverse effect of cytotoxic chemotherapy. It is a potential but rare idiosyncratic effect with any other drug, but there is a recognized association with a number of higher-risk agents, which justify additional vigilance. Myelosuppression is potentially life-threatening because of the infection and bleeding complications of neutropenia and thrombocytopenia. The co-administration of bone marrow protecting or antioxidant herb with the Anti-cancer drug may reduce the drug-induced bone marrow toxicity. The present study aimed to explore the protective effect of RV forte capsules (resveratrol-based formulation) and TCCT (curcumin-based formulation) tablets for their protective potential against Cyclophosphamide-induced bone marrow toxicity in Wistar rats at the dose of 100 and 400 mg/kg dose. In this research work, RV forte TCCT tablets at 400 mg/kg dose showed a significant protective effect against Cyclophosphamide-induced bone marrow toxicity. Significant reduction in histological changes in bone marrow has been observed in treatment groups as compared to only Cyclophosphamide treated groups. Also, the oxidative stress parameters, SOD, CAT, MDA, were found to be reduced, signifying the protective effect of both formulations.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #194 Anti-leucoderma activity of whole plant extract of Cleome chelidonii 2022-04-07T14:16:10+00:00 Kavitha V Shri Vijaya Kirubha T Senthamarai R <p>Skin diseases, especially Leucoderma (or) Vitiligo, is an important widespread disease all over the world. Vitiligo is a skin condition characterized by “White patches resulting from the loss of pigment. <em>Cleome chelidonii</em>&nbsp;Linn. is a traditional plant belonging to the family Capparaceae. It is grown as perennials throughout dry seasons. It has pink rose (or) white color flowers. (Tamil name–Naikakadugu). The leaves of <em>Cleome chelidonii</em> are claimed to have medicinal properties and are generally known to be used to treat colic, dysentery, headache, otitis, and rheumatism. The whole plant has also been found to possess multiple therapeutic properties, such as its use of a vermifuge in treating skin diseases including leucoderma, and with anti-inflammatory, antimicrobial, antinociceptive, antipyretic properties. The present study gives the systematic evaluation of the antileuderma activity of the rare plant Cleome chelidonii. Prior to anti-leucodermal activity, the test extracts of <em>Cleome chelidonii</em> were subjected to a skin irritation test performed in rabbits and were found to be non-irritant in nature. Anti-leucoderma activity for the chloroform, acetone, and methanol extracts of <em>Cleome chelidonii</em> were studied in 6J BL C57 Black mice model by the induction of depigmentation by applying 5% 4–hydroxyanisole. From the results, we conclude that the chloroform extract of <em>Cleome chelidonii</em> was found to possess significant Anti-leucoderma activity as compared to the standard drug Psoralen ointment, which produced repigmentation on the 5<sup>th</sup> day of application, and complete repigmentation occurred in the 4<sup>th</sup> week in black mice model.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #195 Synthesis, characterization and antifungal activity of azo coupled dihydropyrimidinones 2022-04-07T14:23:28+00:00 SivaRanjani J Selvinthanuja C Sivakumar T <p>DHPM scaffold were reported to exhibit versatile biological activities. These derivatives possess antimicrobial property which reviewed from the literature. These is a very few study carried out on azo coupled dihydropyrimidinones. So the study focused towards the synthesis of azo coupled DHPMs and the synthesized compounds evaluated for antifungal actions against <em>A. flavus</em>. Synthesis of DHPMs from cyclocondensation between dicarbonyl compounds, diamide, aromatic aldehydes in acidic conditions. Diazonium salt of aromatic amine prepared which then coupled with DHPMs. The synthesized compounds checked to know the composition of elements present. Characterization of compounds done by IR, proton NMR and Mass spectral techniques. Evaluation of in-vitro antifungal activity by well diffusion method. Synthesis of 3, 4-dihydropyrimidinones from cyclocondensation multicomponent one pot synthesis from dicarbonyl compound (acetyl acetone), diamide (urea) and aromatic aldehyde in ethanol in presence of concentrated hydrochloric acid under reflux for 4 h. Synthesis of aryl diazonium salt from 4-nitro aniline. Coupling of aryl diazonium salt with dihydropyrimidinone in presence of 10% NaOH solution. Purification of the synthesized azo coupled DHPM compounds using suitable solvent. The synthesized DHPMs compounds were characterized by IR, NMR, Mass spectral analysis. The azo coupled dihydropyrimidinones compounds were tested for antifungal activity against <em>A. flavus</em>. Antifungal actions of tested compounds were indicated by the zone of inhibition. From the test results, it was found to be all the compounds inhibit the growth of <em>A. flavus</em>. The maximum activity produced by the synthesized azo coupled compounds may be due to the presence of electron donating groups present in the DHPM scaffold coupled with azo derivatives of electron withdrawing group. This study investigated with synthesis, characterization and In-vitro anti-fungal evaluation of azo coupled 3, 4-dihydropyrimidine-2-ones derivatives against <em>A. flavus</em>&nbsp;strain. The compound were synthesized by three steps process. DHPMs prepared from one pot multicomponent condensation of acetyl acetone, urea and various substituted aldehydes in ethanol in presence of Concentrated HCl. All synthesized compounds were obtained in moderate yield. The melting point of synthesized compounds were determined in open capillary method. Purity of compounds checked by thin layer chromatography using silica gel Gas stationary phase and hexane and ethyl acetate as mobile phase. All the compounds were obtained in pure state. The synthesized compounds are characterized by IR, <sup>1</sup>H-NMR and Mass spectral analysis for elemental analysis. The synthesized compounds in-vitro antifungal activity was evaluated against the <em>A. flavus</em>. This study concluded that the azo coupled dihydropyrimidinones possess good antifungal activity against <em>A. flavus</em>&nbsp;cause the aspergillosis.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #196 Soil ecotoxicity prediction against Folsomia candida using 2D-QSAR approach 2022-04-07T14:30:02+00:00 Rahul Paul Mainak Chatterjee Kunal Roy <p>Soil ecotoxicological test is an essential tool for risk assessment of various xenobiotic chemicals. Such tests can be performed using soil invertebrates by exposing them to specified soil contaminating chemicals. Soil invertebrates provide various ecosystem services (i.e., soil transformations are beneficial for mankind). For example, soil invertebrates may influence the mineralization of nutrients in soil organic matter (SOM), affecting the "soil fertility" – an important factor from the agricultural aspect. Hence, soil invertebrates serve as an outstanding biological indicator of the terrestrial ecosystem and overall soil quality, considering their high sensitivity compared to other soil quality indicators (physical/chemical). Therefore, laboratory tests using invertebrates can be considered as the mainstay of ecotoxicological impact assessment. Quantitative and/ or qualitative results elicited from such tests help several regulatory authorities across the globe to determine the ecological risk level of substances and safe exposure limits for human and soil biota. Thus, such valuable information enables governmental regulatory authorities to control manufacturing output and sale of pesticides, to decide threshold limit for safe application of residues to agricultural soils, etc. However, laboratory tests (both in vivo and in vitro) are costly and time-consuming affairs and involve extensive use of animals. Hence, such tests cannot be extended entirely for predicting the toxicity of novel compounds. As a result, an alternative in-silico approach of quantitative structure-activity relationships (QSARs) is used for environmental risk assessment for novel compounds, free of the exhaustive use of test animals under the REACH regulations in the EU. In this background, necessary limited data available from laboratory tests on the soil invertebrate <em>Folsomia candida</em>&nbsp;(C. name: Springtail) were collated from the database of ECOTOX ( Data is collected for the endpoint - pEC<sub>50</sub> only. Samples of 45 chemical compounds were selected, for which chemical descriptors were calculated for each compound. Then the whole dataset is split into a test dataset (11 compounds) and a training dataset (34 compounds), based on Euclidean Distance based approach. Using genetic algorithm, significant descriptors out of all descriptors’ pools were selected. Using these selected set of descriptors both in test set and training set, the Best Subset Selection software ( was run, which gave the best possible combinations of a limited number of descriptors based on desired linear model equation length from which four best models were selected based on their internal and external validation metrics. Four partial least squares (PLS) models were built based on those four multiple linear regression (MLR) models. These four models were then used in Intelligent Consensus Predictor version 1.2 (PLS version) to get the final consensus model, built using the best selection of predictions (compound-wise) from four ‘qualified’ individual models. Both internal and external validations metrics of this consensus model are well-balanced and within the acceptable range as per the OECD criteria, which is reconfirmed by predictions made through the Chemical Read-Across method. From the aforementioned parameters, a certain conclusion on general contribution can be made: Firstly, with an increase in the number of electron donor groups and consequent hydrogen bond interactions, the toxicity (pEC<sub>50</sub>) increases. The soil toxicity can increase with an increase in the aqueous solubility of compounds. However, on the contrary, if bulky groups are present amidst the polar groups, toxicity is observed to decrease due to steric hindrance and increased lipophilicity. Secondly, it was seen from the data that when the number of five-membered rings increases, then toxicity (pEC<sub>50</sub>) increases. Lastly, a negative correlation was observed between the number of substitutions to aromatic rings and toxicity (pEC<sub>50</sub>).</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #197 Design and discovery of benzamide derivatives as a selective CYP1B1 inhibitor; in-silico & in-vitro approach 2022-04-07T14:39:00+00:00 Mohd Usman Mohd Siddique Azim Zakir Ansari Mrunali Patil Sameer N Goyal <p>The aim of this work was to design a small molecule inhibitor of CYP1B1 enzyme by computational approach and performing synthesis and biological evaluation of a small library of synthesized molecules. Selective inhibitors of CYP isoforms are important in the treatment of cancers caused by hormonal imbalance. This could avoid the severe mechanism-based toxicities or off-target effect as CYP1B1 expresses in cancerous tissues, not in a healthy one. Metabolites of estradiol and polyaromatic hydrocarbons generated due to CYP1B1 activity were reported to be oncogenic. Here, we used the combined comparative shape and electrostatic and molecular docking approach towards the design of selective CYP1B1 inhibitors. The designed benzamide derivative displayed Tanimoto shape 0.847 and Tanimoto electrostatic 0.882, respectively, with known CYP1B1 inhibitor. The molecular docking studies also showed the identical pattern of binding as that of reference molecules. Encouraged by these results we synthesized the eight benzamide derivatives that will be screened against various isoforms of CYPs in Sacchrosomes<sup>TM</sup>, ‘Live Yeast cells’ and ‘Live human cells.’ The small molecule benzamide derivative as a selective CYP1B1 inhibitor has been designed by a combined approach of shape and electrostatic based comparative study of reported potent inhibitor with a small library of designed benzamide derivatives followed by molecular modeling studies. The top HIT molecule was then synthesized, and their different derivatives were also made. Further, all molecules will be screened for their potent and selective CYP1B1 inhibitory activity using various isoforms of the CYP1B1 enzyme.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #198 A mechanistic approach to explore the neuroprotective potential of zonisamide in chronic constriction injury-induced animal model of neuropathy 2022-04-07T16:03:27+00:00 Abdulla Sherikar Aman Upaganlawar Chandrashekhar Upasani <p>Currently, the epidemiological data showed that almost 6.9% to 10% of individuals suffer from neuropathic pain. Presently, diagnosis of neuropathic pain is done based upon history, physical examination, and category of pain. Due to difficulty in doing a clinical screening of a huge number of populations and an undeveloped gold standard for screening methods, neuropathic pain is considered a heterogenic medical condition. Peripheral neuropathy is a hallmark of chronic neuronal disease becoming challenging to treat. Currently, the antiepileptic agents are employed as first-line agents for its treatment, so the present work was undertaken to explore the beneficial uses of zonisamide against chronic constriction injury in rats. After the development of peripheral neuropathy by chronic constriction injury (CCI) around the sciatic nerve, rats were treated with intraperitoneal administration of zonisamide 40 mg/kg/day for two weeks. At the end of the study, the hallmark parameters like allodynia, hyperalgesia, oxidative stress parameters, and inflammatory markers were evaluated. The post-surgery two weeks (14 days) treatment with Zonisamide significantly attenuated the CCI-induced allodynia and hyperalgesia, modulated oxidative stress, and decreased level of inflammatory markers. This study protocol suggests that Zonisamide attenuated the CCI-induced sciatic nerve dysfunction, probably mediated through its antioxidant, analgesic, anti-inflammatory, and neuroprotective actions.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #199 Structure aided drug development of potential antiviral agents against chikungunya virus 2022-04-07T16:47:30+00:00 Sayali Ayare Harwin Khanguda Kaur Jasbir Singh Jyotinder Kaur Meena Kanyalka <p>The recent upsurge of viral infections due to viruses such as Ebola, Chikungunya, Zika, Nipah, SARS-CoV-2 led to global distress that drove the focal point on the development of promising antiviral molecules. We have centered our research mainly on the development of potential molecules against Chikungunya which outbreaks into a severe epidemic. Although there is no definite treatment, studies have indicated that drugs like Chloroquine, Arbidol, Thiazolidine derivatives inhibit viral cell entry; out of which Nitazoxanide is reported to be efficient against Chikungunya. It consists of a thiazole scaffold common in many experimental and approved drugs. Consequently, the versatile pharmacological nature of the thiazole scaffold led us to choose it for further exploration along with isostere five-membered heterocycles – imidazole and oxazole for screening of activity against entry spike glycoprotein (E2) of Chikungunya virus. In-silico molecular docking was used to focus on binding interactions of the designed thiazole and analogous scaffolds in the glycoprotein complex of the Chikungunya virus. Docking software Glide7.4 with Maestro11.1 and ADME screening using QikProp5.1 (Schrodinger, LLC, New York, NY, 2019) were used for this purpose. The set of drug analogs showing promising interactions was synthesized and characterized using FTIR and NMR. The in-vitro evaluation is ongoing. It was revealed from docking studies that all designed molecules showed potential interactions with the E2 glycoprotein of the Chikungunya virus. Out of these molecules, some which showed stronger interactions were synthesized and subjected to ADME studies, which also displayed optimistic results. The in-silico studies concluded that all three series of thiazole, oxazole, imidazole showed properties likely to that of established drugs. From this, it can be inferred that good antiviral activity against chikungunya might be possessed by furanamido analogs of thiazole, oxazole, imidazole.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #200 Formulation and evaluation of gastro-retentive tablet by using RAFT forming system 2022-04-07T16:52:03+00:00 Vikas Mirashe <p>The study was conducted to develop a gastro-retentive tablet of carvedilol by raft forming system for the treatment of hypertension. It was achieved by the formulation of carvedilol tablets using different polymers in variable ratios. The raft drug delivery provides drug delivery for more than eighteen hours by forming a gel-like structure. Preparation of gastro retentive tablet using raft forming system in wet granulation method. Ingredients mentioned carvedilol, sodium alginate, sodium bicarbonate, chitosan were used to prepare Carvedilol gastro retentive tablets. All ingredients except the binder and lubricant were mixed thoroughly and passed through sieve 80. PVP K30 was dissolved in a sufficient quantity of propranolol and added to a powder mixture to prepare dough wet mass. The prepared wet mass was passed through a 10 sieve. The granules were allowed to dry in a hot air oven at 70 °C for 1 h and then resifted through a 44 sieve. To the granule’s talc, and magnesium stearate were added. Granules were compressed to a tablet using an 8 mm diameter flat punch with the help of a rotary tablet compression machine. From the results of research work, it can be concluded that raft forming gastro retentive tablets of Carvedilol can be successfully prepared by wet granulation method by sodium alginate, chitosan, sodium bicarbonate. Among all the formulations, it is concluded that gastro retentive tablets prepared using chitosan (10%) by raft forming method gave better results due to increased gastric residence time and its absorption. Hence, this formulation will be helpful to achieve good bioavailability and better therapeutic activity. Prepared gastro-retentive tablets were evaluated for hardness, friability, weight variation, drug content, raft strength, acid neutralization capacity, in-vitro release study, and short-term stability studies. From all formulations containing sodium alginate 16%, sodium bicarbonate 7.5%, chitosan 10%, and sufficient concentration of tale and magnesium stearate was selected as optimized formulations, chitosan 10% show comparatively good release for 12 h.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #202 Memory enhancing effects of citrullus seed oil in mice are correlated with antioxidant protection and acetylcholinesterase inhibition 2022-04-07T16:54:15+00:00 Rahul Adnaik <p>Brain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. Several recent studies have suggested that higher intake and blood levels of omega-3 fatty acids may help to reduce the risk of age-related cognitive decline, dementia, and Alzheimer’s disease. The major dietary sources of these fatty acids are fish and shellfish from both salt water and fresh water. EPA and DHA can also be synthesized from the elongation and desaturation of alpha-linolenic acid, which is present in some vegetable oils. Oxidative stress significantly contributes to neuronal damage seen in cases of cognitive impairment and Alzheimer’s disease by depleting the brain of vulnerable, highly unsaturated fatty acids (e.g., EPA and DHA). Some researchers suggest that by replenishing brain cells with EPA and DHA via higher intake levels, individuals may help protect themselves against cognitive decline to a significant degree. These findings prompted us to investigate the effects of daily, 7-day, oral administration of <em>Citrullus vulgaris</em>&nbsp;seed oil on learning and memory by interoceptive behavioral models (passive avoidance test and elevated plus maze), their brain AChE activity, and oxidative status. Whole-brain homogenates were collected for examination of brain oxidative markers and acetylcholinesterase (AChE) activity. Results showed that the short-term supplementation of both healthy adult and aged mice significantly exhibited improvement in learning and memory in the passive avoidance test and attenuated brain oxidative stress markers. Furthermore, AChE activity was significantly decreased only in adult mice. Thus, we showed, for the first time, the significant cognitive enhancement conferred by <em>C. vulgaris</em>&nbsp;seed oil administration in mice is more closely related to antioxidant reinforcement.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #203 Green synthesis of benzimidazole using QbD approach 2022-04-07T16:56:22+00:00 Kumar Pratyush Alpana Asnani Bhushan Dravyakar Priya Dule <p>Drug discovery is one of the key interests of several researchers, profit organizations, and non-profit organizations. The discovery process usually takes a long duration of time out which a greater percentage of the time, money is used for the synthesis of an efficient and safe molecule. The current research approaches are mostly focused on the development of new molecules by harming mother nature to the least possible extent. The methodology includes optimization of the novel method for synthesis of benzimidazole, a potent bioactive agent using a quality by design approach. The novel method was successfully developed for the synthesis of benzimidazole. The optimization of the developed method was carried out by using the QbD approach, and the optimized parameter was 180 w for 7.5 min. The novel method developed by using the green chemistry approach was found to be efficient than the conventional method.</p> <p><img src="blob:" /></p> <p>Fig. Comparison of synthesis of benzimidazole by conventional and green method</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #204 Phytochemical analysis and antimicrobial screening of Sesuvium portulacastrum L. from Pichavaram mangrove forest 2022-04-07T17:25:03+00:00 Priya Dharshini Shanmugam Pragathi K S Akilandeshwari S Senthamarai R <p>The increasing number of antibiotic-resistant bacteria necessitates the development of natural antimicrobial substances with minimal health risks. Medicinal plants’ antimicrobial effects are becoming more well known around the world. Mangroves are biochemically distinctive in that they create a wide range of novel natural compounds, including steroids, triterpenes, saponins, flavonoids, alkaloids, and tannins. Plants from the mangrove family have long been utilized in medicine. Ethanol was used to make a plant extract of <em>Sesuvim portulacastrum</em>&nbsp;in this investigation. Some antibiotic-resistant and harmful bacterial and fungal species were investigated for antimicrobial activity. The extract was evaluated at different concentrations (25, 50, 75, and 100 µL). As inhibition zones, the 100 µL concentration produced the best results. The inhibition zones of <em>Sesuvium portulacastrum</em>&nbsp;L. plant extract ranged from 8 mm to 18 mm against the majority of microorganisms tested. The highest effect was against <em>Aspergillus niger</em>, whereas the least was against <em>Staphylococcus aureus</em>, according to the findings. <em>Sesuvium portulacastrum</em>&nbsp;L. extract contains tannins, alkaloids, glycosides, flavanoids, and terpenoids, according to the qualitative phytochemical study. The current investigation found that <em>Sesuvium portulacastrum</em>&nbsp;L. extract has a significant antimicrobial impact against a number of diseases.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #205 Development and characterization of Sitagliptin microsphere for controlled release and better patient compliance 2022-04-07T17:32:22+00:00 Abhishek Jana Pintu Kumar De Bohnisikha Maity <p>In the last few decades, it has been observed that the diabetes population is increasing around the world. Apart from insulin injections, various oral antihyperglycemic medications are available, like sitagliptin, to increase insulin production to control diabetic conditions. But sitagliptin has a very short biological half-life of 8-14 h, and only 38% drug binds to plasma protein; also, 79% drug is eliminated from the body unchanged from the urine, due to which patients required multiple dosing. The objective of the present study was to develop a microsphere with a hydrophobic primary polymer like ethyl cellulose (EC) and hydrophilic secondary polymer HPMC to sustain the drug release and to control the desired release rate with an increase in the duration of drug action. With the primary polymer, another copolymer is used to fabricate a controlled release microsphere. For microsphere preparation emulsion solvent evaporation (ESE) method was used here; in this method, drug and polymer first dissolved in organic phase then added in oil with constant stirring to evaporate organic phase.ESE method provides %yield from a range of 72% to 95% in different variable batches. Entrapment efficiency (EE) is also studied to have in-between 69% to 80% range. Formulation F5 polymer copolymer ratio of 1:1 showing 30% burst release within 15 min on dissolution study which is quite effective to reach the faster onset of action and releases 69% drug up to 6 h of study. FTIR data indicates selected polymers are not interacting with sitagliptin which otherwise can deteriorate its therapeutic efficacy. Microspheres are further characterized on various tests like Scanning electron microscopy (SEM), dissolution kinetics, floating capacity, micromeritics property. EE data and % yield data showing ESE method is suitable for making microspheres with minimum loss of raw materials. Dissolution study showing burst release for faster onset of action followed by sustained release of the drug.</p> <p><img src="blob:" /></p> <p>Fig. Dissolution data comparison for different formulation</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #206 Synthesis and docking studies of metal complexes of Co(II) and Cu(II) 2022-04-07T17:36:55+00:00 Supriya Unavane Hemant Kumar Jain <p>Metal complexes of organic compounds are being widely studied for various pharmacological activities, especially as anticancer and antimicrobial agents. Schiff bases are very good ligands that can readily form complexes with various metals like Pt, Ru, Au, Ag, Fe, Co, Cu, etc. Cinnamaldehyde is reported to possess anticancer and antimicrobial activities. Thiazoles form a part of drugs like ritonavir, sulfathiazole, etc. A combination of these two moieties would increase the potency of the compounds. Herein, we report Schiff base ligands synthesized from cinnamaldehyde and 4-substituted-2-aminothiazoles. Further, these ligands were complexed with cobalt and copper salts to form metal complexes. To synthesize and perform docking studies of Co(II) and Cu(II) metal complexes of thiazole containing Schiff bases. Schiff bases were synthesized from cinnamaldehyde and 4-substituted 2-aminothiazoles. These were treated with the alcoholic solution of metal salts to form colored metal complexes. The synthesized complexes were characterized using FTIR and mass spectrometry. Docking studies of the ligands and metal complexes were carried out to study and compare their anticancer and antimicrobial activities. The metal complexes were successfully synthesized and characterized. From the docking studies, it was evident that these complexes possess good K<sub>i</sub> value. The synthesized metal complexes could show good anticancer and antimicrobial activity.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #207 Formulation and characterization of fast dissolving oral films delivering model antihyperglycemic drug 2022-04-07T17:40:06+00:00 Muniraj Bhattacharya Pintu Kumar De <p>Fast dissolving oral films are drug delivery systems of the new day having one of the highest patient compliance, safety &amp; are economical than most other dosage forms. Hydrophilic polymers, when in contact with water, get hydrated and thus show drug release if used as a vehicle. Hydrophilic polymers also show an adherence property post hydration. Thus the hydrating and adhering properties of hydrophilic polymers make it most suitable for producing fast dissolving oral film. Fast dissolving oral films are made to be administered into the buccal cavity of humans as the buccal cavity if having saliva and saliva helps to hydrate the films leading to drug release. The buccal cavity in humans has a very high amount of blood supply system, thus aiding in faster drug entrance into the blood circulation. The fast dissolving oral films are capable of initiating drug release within seconds, without chewing and drinking. The instant bioavailability achieved bypassing the fast pass metabolism also adds as a salient feature. Various compositions of different polymers lead to differences in the drug release rate of the films. Polymers such as hydroxypropyl methylcellulose (HPMC); polyvinyl alcohol (PVA); ethyl cellulose; sodium carboxymethyl cellulose are some common hydrophilic polymers that are used to produce fast dissolving oral films. Drugs with a shorter half-life and having the small intestine as their main site of absorption and maintenance of adequate plasma levels of the drug can be achieved by systemic drug delivery, for active pharmaceutical ingredients having high solubility and low permeability resulting to produce low bioavailability. Solvent casting, semi-solid casting; hot-melt extrusion; solid dispersion extrusion are some common methods of production of fast dissolving oral films. Immediate onset of action in a shorter period with improved bioavailability marked fast dissolving oral film, a dosage form of choice. Though the films are not a good choice for water-insoluble drugs. Five different formulations with HPMC and PVA as polymers in different raions are prepared using the solvent casting method. Propylene glycol is used as the plasticizer. Films are cast in molds, dried, and kept in moisture-free storage away from sunlight at room temperature. After producing the fast dissolving oral films, they are passed through a series of evaluations such as weight (ranging between 0.216-0.152 gm), thickness (ranging between 0.11-0.074 mm), folding endurance (ranging between broken at 185.5 to 250 not broken), swelling% (ranging between 651.61 to 1020%), drug content (ranging between 98 to 99%), disintegration time (ranging between 15 sec to 50 sec) and in-vitro drug release (ranging between 59 to 83% drug release at 15 min). All data were recorded in triplicates and found that all films passed the required evaluations. It was found that the amount of increase in hydroxypropyl methylcellulose gives faster drug release compared to polyvinyl alcohol.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #212 Simultaneous estimation of antihypertensive agents by two different UV methods 2022-04-07T17:43:49+00:00 Leena Sawaikar Ketaki Usgaonkar <p>The aim of this study is to develop and validate two analytical methods for the simultaneous estimation of Amlodipine besylate (AMLO) and Hydrochlorothiazide (HCTZ) using simultaneous equations method and absorption ratio method by UV spectrophotometry. Method A involved the simultaneous equations method. The two wavelengths, 238 nm (λ<sub>max</sub> of AMLO) and 271 nm (λ<sub>max</sub>&nbsp;of HCTZ), were chosen for the formation of simultaneous equations method. Beer Lambert’s law was obeyed in the concentration range of 5-35 μg/mL for amlodipine besylate and hydrochlorothiazide, respectively with a correlation coefficient (r<sup>2</sup>) greater than 0.990. For Q absorbance ratio method, 253 nm (isosbestic point) and 271 nm (λ<sub>max</sub> of HCTZ) were chosen as the two wavelengths for analysis. A concentration range of 5-35 μg/mL for AMLO and HCTZ, respectively, with a correlation coefficient (r<sup>2</sup>) greater than 0.990, was selected as per beer’s law. The developed method validation was done as per ICH guidelines. The % assay of AMLO and HCTZ were found to be 99.670 % and 101.086% by simultaneous equations method and 98.038% for amlodipine and 100.230% by absorption ratio method, which were within the acceptable limit. The developed methods were simple, sensitive, accurate, precise, and robust and can be used for the simultaneous estimation of the two drugs in tablet formulation.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #213 Probable role of immunity booster herbal drugs in Covid-19 from Abha, Aseer region, Saudi Arabia 2022-04-07T17:49:29+00:00 Shehla Nasar Mir Najib Ullah <p>The outbreak of the novel coronavirus disease (Covid-19) emerged in December 2019; from (Wuhan) China has now become an emergency of major international concern. It is a highly contagious disease that is believed to be a mutated form of SARS (2002) and MERS (2012) virus, causing approximately 3.7% mortality rate worldwide. The main cause of mortality is clusters of severe respiratory illness similar to SARS. The transmission of the novel coronavirus occurs via droplets of human sputum, contaminated hands, and surfaces. The incubation time has been described to be 02-14 days, and for the treatment of Covid-19, early diagnosis, quarantine, and supportive care are essential for patients. The aim here is to focus on the possible role of immunity booster herbal drugs to develop a better immunity that helps to protect humans from Covid-19 infections. Immunity-boosting herbal drugs and their purified products have shown positive results and may have a role as a supportive treatment against Covid-19 infections. Some herbal drugs like <em>Mentha longifolia</em>, <em>Plectranthus amboinicus</em>, and <em>Allium sativum</em>&nbsp;are known immunity-boosting drugs commonly used as folklore medicines in the Aseer region of Saudi Arabia. The drugs mentioned above may give promising protection against Covid-19 infection if the research is focused on these herbals. Apart from these mentioned drugs, <em>Zingiber officinalis</em>, <em>Curcuma longa</em>, and <em>Ocimum sanctum</em>&nbsp;may play their therapeutic roles for Covid-19 by treating lungs associated diseases. Immunity booster herbals could be a valuable tool for the development of active compounds for protection against Covid-19 infection and may contribute to the mitigation of the spread of the pandemic.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #215 Formulation and solubility analysis of amorphous solid dispersions of Diclofenac sodium: A comparative study 2022-04-07T17:52:45+00:00 Mahalaxmi Rathnanand Bhoomika Shetty Divya Dhatri Rajeshwari Roychawdhury <p>Amorphous solid dispersions (ASDs) are aimed to improve the solubility of poorly water-soluble drugs. The purpose of the present study was to determine the technique which provided maximum solubility of ASD of Diclofenac sodium with suitable polymer and buffer media. ASDs can be prepared using various methods. In this experiment, ASDs of BCS Class 2 drug Diclofenac sodium were prepared using various methods like solvent evaporation with heat and without heat, rotary evaporation using Rota vapor, and Hot Melt Extrusion. Three different polymers HPMC, PVP, and Soluplus, were used in the preparation of ASDs. ASDs obtained were characterized using analytical techniques like FT-IR and DSC. Solubility study was conducted by dissolving the obtained ASDs in buffers with pH 1.2, 6.8, 7.4, and water. Samples were kept in Rotaspin for 48 h, later these were centrifuged, and the supernatant was analyzed using UV/Vis spectrophotometer. Graphs were plotted for data obtained from solubility analysis and were compared. When all data were compared, ASDs prepared using HME with three polymers showed improved solubility in pH 7.4 buffer and water. By this, we could conclude that HME was the best method to prepare ASDs of Diclofenac sodium.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry #216 Kinetic study of melatonin by validated stability indicating HPTLC method 2022-04-07T17:58:15+00:00 Shubhangi V Sutar Sachinkumar V Patil <p>Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product. Some degradation products and impurities may even have toxic effects. Therefore, it is very important to develop proper stability indicating method for Melatonin which possibly be used for stability testing and routine analysis. A rapid, sensitive with stability indicating HPTLC method be developed and validated to study degradation kinetics of Melatonin (MT) in alkaline, acidic and oxidative conditions. All degraded samples be chromatographed on Silica gel 60F 254 plates, developed using solvent system toluene: methanol: formic acid (7:3:0.1) and scanned at 290 nm.The developed method was validated as per ICH guidelines using validation parameters such as specificity, linearity and range, precision, accuracy, LOD and LOQ. Degradation kinetics of MT in acidic and alkaline medium was studied by degrading it underneath three distinct concentrations of alkali and acid at three different time interval. Degradation of melatonin into the alkaline and acidic medium was found to follow first order kinetics. Acid, alkaline and oxidative degradation reactions studied to determine the rates of the reaction and susceptibility of melatonin. The HPTLC technique established in this work is precise, specific, and accurate stability indicating statistical analysis proves the method is suitable for analysis of melatonin. Melatonin degraded in acidic, alkaline, oxidative stress conditions. Alkaline and acidic degradation of melatonin followed first order kinetics and higher degradation was found in 1N NaOH and 1N HCl.</p> 2022-07-20T00:00:00+00:00 Copyright (c) 2022 Journal of Pharmaceutical Chemistry