A QSAR Study on Some Series of Anti-Hepatitis C Virus (HCV) Agents

Hepatitis C virus (HCV) is a major human pathogen, infecting an estimated 170 million persons worldwide, roughly five times the number infected by HIV type 1. A substantial fraction of these HCV infected individuals develop serious progressive liver disease, including cirrhosis and hepatocellular carcinoma. The current treatment regimen suffers from various side effects. These limitations encourage the search of more effective HCV inhibitors. To achieve this objective a quantitative structure-activity relationship (QSAR) study has been made on three different series of anti-HCV agents that are comprised of pyrrolo[2,3-d]pyrimidine nucleoside derivatives, benzimidazole-coumarin conjugates, and ribonucleoside analogues, respectively. The QSAR analysis reveals that anti-HCV potencies of these series of compounds are controlled by a topological parameter (Kier's first order valence molecular connectivity index 1χv), lipophilicity, and the molar refractivity of the compounds, respectively. Based on these results, the mechanisms of drug-receptor interactions of these compounds are discussed, which may be of great help to design and develop more anti-HCV agents.