A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-xL/BakBH3 domain peptide interaction.
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.
Litaudon
Marc
M
Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, UPR2301, CNRS, 91198 Gif-sur-Yvette, France. litaudon@icsn.cnrs-gif.fr
Bousserouel
Hadjira
H
Awang
Khalijah
K
Nosjean
Olivier
O
Martin
Marie-Thérèse
MT
Dau
Marie Elise Tran Huu
ME
Hadi
Hamid A
HA
Boutin
Jean A
JA
Sévenet
Thierry
T
Guéritte
Françoise
F
D008296:Malaysia; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism
D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; C548770:meiogynin A