Embellicines A and B: Absolute Configuration and NF-kappa B Transcriptional Inhibitory Activity

W Ebrahim, A H Aly, V Wray, A Mandi, M H Teiten, F Gaascht, B Orlikova, M U Kassack, W H Lin, M Diederich, T Kurtan, A Debbab, P Proksch

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26 Scopus citations

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-kappa B transcriptional activity, indicating that inhibition of NF-kappa B 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.
Original languageEnglish (US)
Pages (from-to)2991-2999
Number of pages9
JournalJournal of Medicinal Chemistry
DOIs
StatePublished - 2013

Keywords

  • acremonium-zeae
  • activation
  • alkaloids
  • cancer
  • cells
  • chronic lymphocytic-leukemia
  • endophytic fungus
  • metabolites
  • natural-products
  • therapeutic target

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