Molecular docking study of P4-Benzoxaborolesubstituted ligands as inhibitors of HCV NS3/4A protease

Abstract

NS3/4A protease is an important emerging target for the cure of hepatitis C. There are many inhibitors of HCV NS3/4A protease that are passing through the clinical improvement indicating momentous reduction in the viral infection rate of patients. In this study molecular docking via MOE-Dock program was used to evaluate binding interactions of ligands with HCV NS3/4A protease. The docking and experimental results were found in good correlation. The best conformations of ligands were analyzed for binding interactions with the residues of binding cavity of NS3/4A protease. The valuable binding interactions and docking scores were observed for compounds 01, 05, 06, 07, 08 and 09.

Keywords: Binding interactions; HCV NS3/4A protease; Molecular Docking; inhibitors.

Figure 1

2D Structures of retrieved ligands, (a) compound 01,(b) compound 02, (c) compound 03, (d) compound 04, (e) compound 05, (f) compound 06, (g) compound 07, (h) compound 08, (i) compound 09, (j) compound 10, (k) compound 11

Figure 2

Blue Native co-crystallized ligand and red docked ligand.

Figure 3

A correlation graph for docking predicted activity and IC50 values.

Figure 4

The 2D pictures of the docked conformations of most active compounds, (a) compound 05, (b) compound 02, (c) compound 01, (d) compound 09, (e) compound 06, (f) compound 08, (g) compound 07.