(+)- and (-)-Ecarlottones, Uncommon Chalconoids from Fissistigma latifolium with Pro-Apoptotic Activity

J Nat Prod. 2017 Dec 22;80(12):3179-3185. doi: 10.1021/acs.jnatprod.7b00494. Epub 2017 Nov 21.

Abstract

Four new compounds, (+)- and (-)-ecarlottone (1), (±)-fislatifolione (5), (±)-isofislatifolione (6), and (±)-fislatifolic acid (7), and the known desmethoxyyangonin (2), didymocarpin-A (3), and dehydrodidymocarpin-A (4) were isolated from the stem bark of Fissistigma latifolium, by means of bioassay-guided purification using an in vitro affinity displacement assay based on the modulation of Bcl-xL/Bak and Mcl-1/Bid interactions. The structures of the new compounds were elucidated by NMR spectroscopic data analysis, and the absolute configurations of compounds (+)-1 and (-)-1 were assigned by comparison of experimental and computed ECD spectra. (-)-Ecarlottone 1 exhibited a potent antagonistic activity on both protein-protein associations with Ki values of 4.8 μM for Bcl-xL/Bak and 2.4 μM for Mcl-1/Bid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annonaceae / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Chalcones / chemistry*
  • Chalcones / pharmacology*
  • Crystallography, X-Ray
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • KB Cells

Substances

  • Antineoplastic Agents, Phytogenic
  • Chalcones