title: Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-xL/Bak interaction.
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.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, 1, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Leverrier
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Françoise
authors.initials: F
authors.lastname: Guéritte
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D000081:Acetamides / Q000737:chemistry; D019342:Acetic Acid / Q000737:chemistry; D017209:Apoptosis; D020148:Butyric Acid / Q000737:chemistry; D005591:Chemical Fractionation; D019770:Lauraceae / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000302:isolation & purification / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000081:Acetamides; D011084:Polycyclic Aromatic Hydrocarbons; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C553350:kingianin A; D020148:Butyric Acid; C047509:N-ethylacetamide; D019342:Acetic Acid