title: Kingianins O-Q: Pentacyclic polyketides from Endiandra kingiana as inhibitor of Mcl-1/Bid interaction.
abstract: A phytochemical study of the EtOAc-soluble part of the methanolic extract of the bark of Endiandra kingiana led to the isolation of three new pentacyclic kingianins as racemic mixtures, kingianins O-Q (1-3), together with the known kingianins A, F, K, L, M and N (4-9), respectively. The structures of the new kingianins 1-3 were determined by 1D and 2D NMR analysis in combination with HRESIMS experiments. Kingianins A-Q were assayed for Mcl-1 binding affinity. Kingianins G and H were found to be potent inhibitors of Mcl-1/Bid interaction. A structure-activity relationship study showed that potency is very sensitive to the substitution pattern on the pentacyclic core. In addition, in contrast with the binding affinity for Bcl-xL, the levorotatory enantiomers of kingianins G, H and J exhibited similar binding affinities for Mcl-1 than their dextrorotatory counterparts, indicating that the two anti-apoptotic proteins have slightly different binding profiles.
authors.affiliation: Centre for Natural Product Research and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mohamad Nurul
authors.initials: MN
authors.lastname: Azmi
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Univ. Paris-Sud 11, av. de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Péresse
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Univ. Paris-Sud 11, av. de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Remeur
authors.affiliation: Centre for Natural Product Research and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Gomathi
authors.initials: G
authors.lastname: Chan
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Univ. Paris-Sud 11, av. de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS-ICSN UPR2301, Univ. Paris-Sud 11, av. de la Terrasse, 91198 Gif-sur-Yvette, France. Electronic address: marc.litaudon@cnrs.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.affiliation: Centre for Natural Product Research and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: khalijah@um.edu.my.
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
mesh_terms: D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D019770:Lauraceae / Q000737:chemistry*; D015394:Molecular Structure; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000302:isolation & purification; D061065:Polyketides / Q000737:chemistry* / Q000302:isolation & purification; D013329:Structure-Activity Relationship
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010936:Plant Extracts; D011084:Polycyclic Aromatic Hydrocarbons; D061065:Polyketides; C553350:kingianin A
keywords: Anti-apoptotic protein; Endiandra kingiana; Kingianins; Lauraceae; Mcl-1/Bid