Flavonoid-triazolyl hybrids as potential anti-hepatitis C virus agents: Synthesis and biological evaluation

Eur J Med Chem. 2021 Jun 5:218:113395. doi: 10.1016/j.ejmech.2021.113395. Epub 2021 Mar 31.

Abstract

A series of flavonoid-triazolyl hybrids were synthesized and evaluated as novel inhibitors of hepatitis C virus (HCV). The results of anti-HCV activity assays showed that most of the synthesized derivatives at a concentration of 100 μg/mL inhibited the generation of progeny virus. Among these derivatives, 10m and 10r exhibited the most potent anti-HCV activity and inhibited the production of HCV in a dose-dependent manner. Interestingly, 10m and 10r had no significant inhibitory effect on viral translation or replication. Additional action mechanism studies revealed that the most potent compounds, 10m and 10r, significantly inhibited viral entry to 34.0% and 52.0%, respectively, at 10 μM. These results suggest further effective application of 10m and 10r as potential HCV preventive agents.

Keywords: Anti-HCV activity; Flavonoid-triazolyl hybrids; HCV entry Inhibitors.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Hepacivirus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Flavonoids
  • Triazoles