#40 Design, synthesis, and anti-inflammatory evaluation of coumarin pyrazoline hybrid with sulphonamide moieties: An in-silico approach



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R, A. .; T, P. .; T, S. .; P, H. .; E, M. .; L, R. . #40 Design, Synthesis, and Anti-Inflammatory Evaluation of Coumarin Pyrazoline Hybrid With Sulphonamide Moieties: An in-Silico Approach. J Pharm Chem 2022, 8.


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 4th 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.

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