Anti-HBV agents. Part 1: Synthesis of alisol A derivatives: a new class of hepatitis B virus inhibitors

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4647-50. doi: 10.1016/j.bmcl.2008.07.012. Epub 2008 Jul 10.

Abstract

A series of alisol A derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities and cytotoxicities in vitro. The preliminary investigation demonstrates that simple modifications of the parent structure of alisol A can produce a number of potentially important derivatives against HBV. The most active anti-HBV compound 6a showed high activities against the secretion of HBV surface antigen (IC(50)=0.024 mM), HBV e antigen (IC(50)=0.028 mM) and remarkable selective indices (SI(HBsAg)>108, SI(HBeAg)>93), which was selected for further evaluation as a novel HBV inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / chemistry
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / pharmacology*
  • Chemistry, Pharmaceutical / methods*
  • Cholestenones / chemical synthesis*
  • Cholestenones / chemistry
  • DNA, Viral
  • Drug Design
  • Hepatitis B / drug therapy*
  • Hepatitis B Antigens / immunology
  • Hepatitis B virus / metabolism*
  • Humans
  • Hydroxyl Radical
  • Inhibitory Concentration 50
  • Models, Chemical
  • Virus Replication / drug effects

Substances

  • Antigens, Viral
  • Antiviral Agents
  • Cholestenones
  • DNA, Viral
  • Hepatitis B Antigens
  • alisol A
  • Hydroxyl Radical