Embellicines A and B: absolute configuration and NF-κB transcriptional inhibitory activity

J Med Chem. 2013 Apr 11;56(7):2991-9. doi: 10.1021/jm400034b. Epub 2013 Mar 29.

Abstract

Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka , an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of extensive one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1. Both embellicines (1 and 2) are cytostatic, cytotoxic, and inhibit NF-κB transcriptional activity, indicating that inhibition of NF-κB may be a possible mechanism of action of these compounds. Embellicine B (2) was the most active compound encountered in this study and acts at nanomolar concentrations without affecting tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Indans / chemistry
  • Indans / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Models, Molecular
  • NF-kappa B / antagonists & inhibitors*
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Transcription, Genetic / drug effects*

Substances

  • Indans
  • NF-kappa B
  • Pyrrolidinones
  • embellicine A
  • embellicine B