Evolution of matrinic ethanol derivatives as anti-HCV agents from matrine skeleton

Bioorg Med Chem Lett. 2017 May 1;27(9):1962-1966. doi: 10.1016/j.bmcl.2017.03.025. Epub 2017 Mar 11.

Abstract

Twenty-two novel 12N-substituted matrinic ethanol derivatives were synthesized and evaluated for their antiviral activities against HCV taking compound 1 as the lead. The SAR study indicated that the shortening of the 11-butyl chain to ethyl chain did not affect the activity significantly. Out of the target compounds, matrinic ethanol 6a demonstrated a potential anti-HCV effect with an EC50 value of 3.2μM and a SI value of 96.6. The free hydroxyl arm in 6a made it possible as a parent structure to prepare pro-drug for the potential application in HCV treatment. This study provided powerful information on further strategic optimization and development of this kind of compounds into a novel family of anti-HCV agents.

Keywords: Druglike; Hepatitis C virus; Matrinic ethanol; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacokinetics
  • Alkaloids / pharmacology*
  • Animals
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacokinetics
  • Drugs, Chinese Herbal / pharmacology
  • Ethanol / analogs & derivatives
  • Ethanol / pharmacokinetics
  • Ethanol / pharmacology
  • Hepacivirus / drug effects*
  • Hepacivirus / growth & development
  • Hepatitis C / drug therapy
  • Humans
  • Matrines
  • Quinolizines / chemistry*
  • Quinolizines / pharmacokinetics
  • Quinolizines / pharmacology*
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Antiviral Agents
  • Drugs, Chinese Herbal
  • Quinolizines
  • Ethanol
  • Matrines