title: Protein kinase and HDAC inhibitors from the endophytic fungus Epicoccum nigrum.
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 IC50 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.
authors: Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Düsseldorf , Universitätsstrasse 1, Geb. 26.23, 40225 Düsseldorf, Germany.
authors: Mustapha
authors: M
authors: El Amrani
authors: Daowan
authors: D
authors: Lai
authors: Abdessamad
authors: A
authors: Debbab
authors: Amal H
authors: AH
authors: Aly
authors: Karsten
authors: K
authors: Siems
authors: Carole
authors: C
authors: Seidel
authors: Michael
authors: M
authors: Schnekenburger
authors: Anthoula
authors: A
authors: Gaigneaux
authors: Marc
authors: M
authors: Diederich
authors: Daniel
authors: D
authors: Feger
authors: Wenhan
authors: W
authors: Lin
authors: Peter
authors: P
authors: Proksch
mesh_terms: D001203:Ascomycota / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D027541:Mentha / Q000382:microbiology*; D015394:Molecular Structure; D009018:Morocco; D019906:Nuclear Magnetic Resonance, Biomolecular; D018515:Plant Leaves / Q000382:microbiology; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011494:Protein Kinases; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D061065:Polyketides; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases