Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-xL/Bak interaction.

Aurélie Leverrier, Khalijah Awang, Françoise Guéritte, Marc Litaudon

Index: Phytochemistry 72(11-12) , 1443-52, (2011)

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Abstract

An in vitro biological screening of Malaysian plants allowed the selection of several species with a significant binding affinity for the antiapoptotic protein Bcl-xL. The chemical investigation of Endiandra kingiana led to the isolation of a series of polyketides named kingianins A-N, having a pentacyclic carbon skeleton described for the first time in nature. Fourteen compounds were isolated as racemic mixtures, and characterized by mass spectrometryand extensive one- and two-dimensional NMR spectroscopy. The (-) and (+) enantiomers of kingianins A and G-L were separated using chiral HPLC, and the absolute configuration of four of them was clearly established by CD analysis. The levorotatory enantiomers showed the more potent binding affinity for Bcl-xL with Ki ranging from 1.0 to 12μM.Copyright © 2011 Elsevier Ltd. All rights reserved.