A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-xL/BakBH3 domain peptide interaction

J Nat Prod. 2009 Mar 27;72(3):480-3. doi: 10.1021/np8006292.

Abstract

In an effort to find potent inhibitors of the antiapoptotic protein Bcl-xL, a systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts. The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was selected for its interaction with the Bcl-xL/Bak association. Bioassay-guided purification of this species led to the isolation of two new dimeric sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of 10.8 +/- 3.1 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Malaysia
  • Molecular Structure
  • Plant Bark / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification*
  • Sesquiterpenes / pharmacology*
  • Stereoisomerism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Sesquiterpenes
  • meiogynin A