Novel 4-thiazolidinones as non-nucleoside inhibitors of hepatitis C virus NS5B RNA-dependent RNA polymerase

Arch Pharm (Weinheim). 2015 Jan;348(1):10-22. doi: 10.1002/ardp.201400247. Epub 2014 Dec 2.

Abstract

In continuation of our efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, we synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29-42, together with their synthetic precursors 22-28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 µM. Compound 33, an arylidene derivative, was found to be the most active compound in this series with an IC50 value of 25.3 µM. Molecular docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds.

Keywords: 4-Thiazolidinones; Antiviral agents; HCV NS5B polymerase; Hepatitis C; Molecular modeling.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Computer-Aided Design
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • High-Throughput Screening Assays
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Molecular Structure
  • Protein Conformation
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / metabolism
  • Thiazolidines / pharmacology*
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Thiazolidines
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus