title: Endiandric acid analogues from Beilschmiedia ferruginea as dual inhibitors of Bcl-xL/Bak and Mcl-1/Bid interactions.
abstract: A rapid screening by (1)H and (1)H-(13)C HSQC NMR spectroscopy of EtOAc extracts of Endiandra and Beilschmiedia species allowed the selection of Beilschmiedia ferruginea leaves and flowers extract for a chemical investigation, leading to the isolation of 11 new tetracyclic endiandric acid analogues, named ferrugineic acids A-K (1-11). Their structures were determined by 1D and 2D NMR spectroscopic analysis in combination with HRMS data. These compounds were assayed for Bcl-xL and Mcl-1 binding affinities. Ferrugineic acids B, C, and J (2, 3, and 10) exhibited significant binding affinity for both antiapoptotic proteins Bcl-xL (Ki = 19.2, 12.6, and 19.4 μM, respectively) and Mcl-1 (Ki = 14.0, 13.0, and 5.2 μM, respectively), and ferrugineic acid D (4) showed only significant inhibiting activity for Mcl-1 (Ki = 5.9 μM).
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS , 1 av de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Apel
authors.forename: Charlotte
authors.initials: C
authors.lastname: Gény
authors.forename: Vincent
authors.initials: V
authors.lastname: Dumontet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Birlirakis
authors.forename: Fanny
authors.initials: F
authors.lastname: Roussi
authors.forename: Van Cuong
authors.initials: VC
authors.lastname: Pham
authors.forename: Huong
authors.initials: H
authors.lastname: Doan Thi Mai
authors.forename: Van Hung
authors.initials: VH
authors.lastname: Nguyen
authors.forename: Van Minh
authors.initials: VM
authors.lastname: Chau
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D019770:Lauraceae / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D014744:Vietnam; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000037:antagonists & inhibitors*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors*
chemical_list: D002264:Carboxylic Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C534861:endiandric acid