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Endiandric Acid Analogues from Beilschmiedia ferruginea as Dual Inhibitors of Bcl-xL/Bak and Mcl-1/Bid Interactions

2014; American Chemical Society; Volume: 77; Issue: 6 Linguagem: Inglês

10.1021/np500170v

1520-6025

Cécile Apel, Charlotte Gény, Vincent Dumontet, Nicolas Birlirakis, Fanny Roussi, Van Cuong Pham, Huong Doan Thi, Van Hung Nguyen, Van Minh Chau, Marc Litaudon,

Cancer therapeutics and mechanisms

A rapid screening by 1H and 1H–13C 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).