Development of bivalent oleanane-type triterpenes as potent HCV entry inhibitors

Eur J Med Chem. 2014 Apr 22:77:258-68. doi: 10.1016/j.ejmech.2014.03.017. Epub 2014 Mar 7.

Abstract

The development of entry inhibitors is an emerging approach to the prevention and reduction of HCV infection. Starting from echinocystic acid (EA), a μM HCV entry inhibitor, we have developed a series of bivalent oleanane-type triterpenes which, upon optimization of the length, rigidity and hydrophobicity of the linker, exert dramatically potent enhancement of inhibition with IC50 values extending into the nM level. This study establishes the importance of triterpene natural products as new leads in the development of potential HCV entry inhibitors.

Keywords: Dimer; Echinocystic acid; HCV entry inhibitor; Triterpene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Hepacivirus / drug effects*
  • Hepacivirus / physiology
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / chemistry
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*
  • Virus Internalization / drug effects*

Substances

  • Antiviral Agents
  • Triterpenes
  • oleanane
  • Oleanolic Acid