QSAR and molecular docking directed synthesis and preliminary evaluation of novel non-nucleoside HCV NS5B polymerase inhibitors

4^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing

November 02-04, 2015 Atlanta, USA

V M Patil1, N Masand2 and S P Gupta3

1Bharat Institute of Technology, India 2Lala Lajpat Rai Memorial Medical College, India 3National Institute of Teachers Training and Research, India

Posters-Accepted Abstracts: Med chem

Abstract :

Purpose: The HCV NS5B RNA-dependent RNA polymerase (RdRp) is a central enzyme in the replication of the viral genome and has since become a target of choice for screening and design of small molecule inhibitors for viral replication interference. Experimental description: A series of 4-pyridyl-1H-benzimidazole-4-(N-R1-carboxamide) derivatives was synthesised using two step reaction and NS5B RNA dependent RNA polymerase inhibition assay was used for in vitro evaluation. For in silico screening, the multiple regression analysis based QSAR model and molecular docking studies (FlexX) were used. Results: From in house compound library screening using NS5B polymerase enzymatic assay, we identified some benzimidazole derivatives. The activities were predicted using the QSAR generated models. Along with QSAR predictions, molecular docking studies were used to evaluate binding of these series of compounds at allosteric pocket (AP-1) of NS5B polymerase. Conclusions: The QSAR and molecular docking directed study explains effects of substituents at position 2 and 4 of benzimidazole nucleus for HCV NS5B polymerase inhibition. In vitro preliminary evaluation results in identification of three compounds (4c, 4e, 4f) as promising NS5B inhibitor leads. Docking analysis of NS5B polymerase (AP-1) provided insight for the rational design of novel HCV inhibitors.

Biography :

Email: vaishuwise@gmail.com