Endiandric acid analogues from Beilschmiedia ferruginea as dual inhibitors of Bcl-xL/Bak and Mcl-1/Bid interactions

J Nat Prod. 2014 Jun 27;77(6):1430-7. doi: 10.1021/np500170v. Epub 2014 Jun 5.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology*
  • Lauraceae / chemistry*
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Vietnam
  • bcl-2 Homologous Antagonist-Killer Protein / antagonists & inhibitors*
  • bcl-X Protein / antagonists & inhibitors*

Substances

  • Carboxylic Acids
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-X Protein
  • endiandric acid