UK-1 and structural analogs are potent inhibitors of hepatitis C virus replication

Bioorg Med Chem Lett. 2014 Jan 15;24(2):609-12. doi: 10.1016/j.bmcl.2013.12.012. Epub 2013 Dec 9.

Abstract

The bacterial natural product UK-1 and several structural analogs inhibit replication of the hepatitis C virus in the replicon assay, with IC50 values as low as 0.50 μM. The NS3 helicase has been identified as a possible target of inhibition for several of these compounds, while the remaining inhibitors act via an undetermined mechanism. Gel shift assays suggest that helicase inhibition is a direct result of inhibitor-enzyme binding as opposed to direct RNA binding, and the ATPase activity of NS3 is not affected. The syntheses and biological results are presented herein.

Keywords: Helicase; Hepatitis C; Inhibitor; NS3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology
  • Dose-Response Relationship, Drug
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology
  • Humans
  • RNA Helicases / antagonists & inhibitors
  • RNA Helicases / physiology
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Antiviral Agents
  • Benzoxazoles
  • UK 1
  • RNA Helicases