Protein kinase and HDAC inhibitors from the endophytic fungus epicoccum nigrum

Mustapha El Amrani, Daowan Lai, Abdessamad Debbab, Amal H. Aly, Karsten Siems, Carole Seidel, Michael Schnekenburger, Anthoula Gaigneaux, Marc Diederich, Daniel Feger, Wenhan Lin, Peter Proksch*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

95 Citations (Scopus)

Abstract

A chemical investigation of the endophytic fungus Epicoccum nigrum isolated from leaves of Mentha suaveolens collected in Morocco resulted in the isolation of five new polyketides, epicocconigrones A and B (1 and 2), 3-methoxyepicoccone B (3), 3-methoxyepicoccone (4), and 2,3,4-trihydroxy-6- (methoxymethyl)-5-methylbenzaldehyde (5), together with five known compounds (6-10). The structures of the new compounds were unambiguously determined by extensive analysis of the 1D and 2D NMR and mass spectroscopic data. Compounds 1 and 10 showed potent inhibition of at least 15 protein kinases with IC 50 values ranging from 0.07 to 9.00 μM. Moreover, compounds 1 and 10 inhibited histone deacetylase (HDAC) activities with IC50 values of 9.8 and 14.2 μM, respectively. A preliminary structure-activity relationship is discussed. Interestingly, compounds 1 and 10 exert mainly cytostatic effects in human lymphoma RAJI and U-937 cell lines.

Original languageEnglish
Pages (from-to)49-56
Number of pages8
JournalJournal of Natural Products
Volume77
Issue number1
DOIs
Publication statusPublished - 24 Jan 2014
Externally publishedYes

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