title: A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-xL/BakBH3 domain peptide interaction.
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.
authors.affiliation: Institut de Chimie des Substances Naturelles, 1 Avenue de la Terrasse, UPR2301, CNRS, 91198 Gif-sur-Yvette, France. litaudon@icsn.cnrs-gif.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.forename: Hadjira
authors.initials: H
authors.lastname: Bousserouel
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Olivier
authors.initials: O
authors.lastname: Nosjean
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Marie Elise Tran Huu
authors.initials: ME
authors.lastname: Dau
authors.forename: Hamid A
authors.initials: HA
authors.lastname: Hadi
authors.forename: Jean A
authors.initials: JA
authors.lastname: Boutin
authors.forename: Thierry
authors.initials: T
authors.lastname: Sévenet
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
mesh_terms: 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
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; C548770:meiogynin A