Research Articles
Ajay Kumar Timiri, Syed Hussain Basha, Rana Abdelnabi, Johan Neyts, Pieter Leyssen, Barij Nayan Sinha, Venkatesan Jayaprakash
Availability of X-ray crystal structure of 3C protease of several enteroviruses provided an opportunity for in silico drug design and development approach. Presented study is aimed at designing a novel compound targeting 3C protease of Coxsackievirus (CVB3), which is reported frequently to cause myocarditis in North America and Europe. A pthalimido-sulfonamide derivative (ZINC13799063) was identified through high-throughput virtual screening (HTVS) approach from the top HITs. A small library of phalimido-sulphonamides was enumerated to find a potential LEAD. Compound 17 from the library was found to inhibit CVB3 selectively in cell based antiviral assay at a concentration of EC50=1.0±0.1 µM with a selectivity index of >140. Molecular dynamics study was performed to investigate the selective inhibition of CVB3 over CVB4.
25-34
Sounak Bagchi, Uzma Alia, Faiz Mohammad, Mohd Usman Mohd Siddique
High throughput virtual screening (HTVS) has been proved a successful tool for getting LEADs in drug design and discovery. In an attempt to design new Dengue protease inhibitors, we performed HTVS using Zinc13 database containing 13,195,609 drug-like molecules. ZINC42678127 was identified as potential HIT against Dengue protease. It’s shape and electrostatic complimentary was found to be 0.608 and 0.078, respectively. Qikprop analysis of the compound complied with the Rule of Five (Ro5) and other drug- likeliness properties. Binding mode analysis of docked conformer of ZINC42678127, displayed favorable interaction with the active site residues of DENV protease. The identified HIT has a potential to become a LEAD against Dengue protease.
35-40
Nehla Yahcoob, Baskar Lakshmanan, Jyothi Achuthanandhan, Vijayakumar Balakrishnan
Quinoxaline, an important class of heterocylic compounds drawn greater attention due to their wide spectrum of biological activities. They are considered as an important chemical scaffold for anticancer drug design due to their potential inhibitory activity against C-met tyrosine kinase. C-met kinase inhibitors are a class of small molecules that having therapeutic potential in the treatment of various types of cancers. The present study aims to focus on the chemistry of quinoxaline derivatives, their potential activities against C-met tyrosine kinase, and in-silico screening of designed compounds. A series of twelve compounds were designed and docked against C-met tyrosine kinase for their binding energy. All compounds were found to be interacting well with the protein. Compound NQ1 was found to have good binding energy showing an estimated K i value of 1.1µm. SAR study indicated the presence of an electron withdrawing substitution on benzilidine phenyl ring of quinoxaline greatly improves its binding interaction with the protein.
41-45
