Discovery of potent nucleotide-mimicking competitive inhibitors of hepatitis C virus NS3 helicase

Bioorg Med Chem Lett. 2011 May 1;21(9):2776-9. doi: 10.1016/j.bmcl.2010.09.002. Epub 2010 Sep 6.

Abstract

Among the enzymes involved in the life cycle of HCV, the non-structural protein NS3, with its double function of protease and NTPase/helicase, is essential for the virus replication. Exploiting our previous knowledge in the development of nucleotide-mimicking NS3 helicase (NS3h) inhibitors endowed with key structural and electronic features necessary for an optimal ligand-enzyme interaction, we developed the tetrahydroacridinyl derivative 3a as the most potent NS3h competitive inhibitor reported to date (HCV NS3h K(i)=20 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive / drug effects
  • Drug Discovery*
  • Hepacivirus / enzymology*
  • Hydrazines / chemical synthesis
  • Hydrazines / chemistry*
  • Hydrazines / pharmacology*
  • Protein Binding
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry*
  • Pyrazines / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Viral Nonstructural Proteins / antagonists & inhibitors*

Substances

  • Hydrazines
  • NS3 protein, hepatitis C virus
  • Pyrazines
  • QU663 compound
  • Quinolines
  • Viral Nonstructural Proteins