Anti-HBV agents. Part 2: synthesis and in vitro anti-hepatitis B virus activities of alisol A derivatives

Bioorg Med Chem Lett. 2009 Apr 15;19(8):2148-53. doi: 10.1016/j.bmcl.2009.02.122. Epub 2009 Mar 4.

Abstract

Chemical modifications were performed on hydroxyl groups at C-11,23,24,25 positions and C-13(17) double bond of alisol A for structure-activity relationship study. Forty-one derivatives of alisol A were synthesized and assayed for their in vitro anti-hepatitis B virus (HBV) activities and cytotoxicities. Of them, 14 compounds were active against HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) secretion in HepG 2.2.15 cells, and the most promising compound 25 exhibited high activities against secretion of HBsAg (IC(50)=0.028 mM), HBeAg (IC(50)=0.027 mM) and remarkable selective indices (SI(HBsAg) >90, SI(HBeAg) >93).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology
  • Cell Line
  • Chemistry, Pharmaceutical / methods
  • Cholestenones / chemical synthesis*
  • Cholestenones / pharmacology
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / metabolism
  • Humans

Substances

  • Antiviral Agents
  • Cholestenones
  • Hepatitis B Surface Antigens
  • alisol A