Novel Quinazoline derivatives inhibited HCV Serine protease and viral replication in Huh-7 cells

Abstract

AbstractDrugs against HCV infection are facing several drawbacks such as undesirable side effects, emerging of HCV resistant strains, and high cost of the entire course of treatment. Thus, new active and cost-effective compounds are required to develop effective drugs to combat HCV infection. This study was designed to test the antiviral activity of quinazoline derivatives against HCV infection using HCV protease assay (HCV NS3-4Apro) and cell-based HCV replicon assay. The results showed that some of quinazoline derivatives inhibited HCV NS3-4Apro with IC50 ranged from 42 µM of compound 4 to 150 µM of compound 2. In this study, compound 4 was considered as the best compound lead to developing potent anti-HCV NS3-4Apro inhibitors. The toxic dose of compound 4 was more than 80 µM for 24, 48, and 72 h. Compound 4 showed dose-dependent inhibition against HCV replication with a considerable reduction in Rluc activity at 40 µM. This finding was further investigated by immunostaining that showed the inhibitory effect of compound 4 against HCV NS3-4Apro was dose-dependent. This study identified a unique small molecule compound that could lead to the development of HCV NS3-A4pro inhibitors and would be useful to develop highly effective drugs for HCV infection based on HCV NS3-4A protease inhibition.