Thiazolidone derivatives as inhibitors of chikungunya virus

Eur J Med Chem. 2015 Jan 7:89:172-8. doi: 10.1016/j.ejmech.2014.10.042. Epub 2014 Oct 16.

Abstract

A series of arylalkylidene derivatives of 1,3-thiazolidin-4-one (1-20) were synthesized and tested for their antiviral activity against chikungunya virus (LR2006_OPY1) in Vero cell culture by CPE reduction assay. Five compounds (7-9, 16 and 19) were identified to have anti-ChikV activity at lower micro molar concentration. The compounds 7, 8, 9, 16 and 19 inhibited the virus at 0.42, 4.2, 3.6, 40.1 and 6.8 μM concentrations respectively. Molecular docking simulation has been carried out using the available X-ray crystal structure of the ChikV nsp2 protease, in order to elucidate the possible mechanism of action. Interaction of ligands with ChikV nsp2 protease (PDB Code: 3TRK) suggested the possible mechanism of protease inhibition to act as potent anti-ChikV agents.

Keywords: Antiviral; Chikungunya virus; Molecular docking; Thiazolidinone; nsp2 protease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Chikungunya virus / drug effects*
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Antiviral Agents
  • Thiazoles