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Protein kinase inhibitors and other cytotoxic metabolites from the fungal endophyte Stemphylium botryosum isolated from Chenopodium album

Aly, A.H. and Debbab, A. and Edrada-Ebel, Ruangelie and Muller, W.E.G. and Kubbutat, M.H.G. and Wray, V. and Ebel, Rainer and Proksch, P. (2010) Protein kinase inhibitors and other cytotoxic metabolites from the fungal endophyte Stemphylium botryosum isolated from Chenopodium album. Mycosphere, journal of fungal biology, 1. pp. 153-162.

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Abstract

The endophytic fungus Stemphylium botryosum was isolated from leaves of the medicinal plant Chenopodium album collected in Egypt. Extracts of the fungus grown on rice exhibited considerable cytotoxicity when tested in vitro against L5178Y mouse lymphoma cells. Upon chemical investigation they afforded the macrocyclic lactones curvularin (1) and dehydrocurvularin (2), as well as altersolanol A (3), tetrahydroaltersolanol B (4), stemphyperylenol (5) and macrosporin (6). The structures of all isolated compounds were determined by 1D and 2D NMR spectroscopy and mass spectrometry as well as by comparison with published data. Compounds 1-3 exhibited considerable cytotoxicity against L5178Y cells with EC50 values of 16, 1.4 and 0.6 μM, respectively, whereas the remaining compounds showed only modest activity. All compounds were further tested for protein kinase inhibitory activity in an assay involving 24 different kinases. Compound 3 was the most potent inhibitor displaying EC50 values ranging between 1.9 and 29.4 μM toward individual kinases, followed by 6 (EC50 = 2.3 - 27.1 μM). Compounds 4 and 5 showed moderate activity, while 1 and 2 were inactive.

Item type: Article
ID code: 32604
Keywords: cytotoxic activity, endophytic fungi, natural products, protein kinase, Therapeutics. Pharmacology
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 17 Aug 2011 14:19
    Last modified: 04 Oct 2012 13:49
    URI: http://strathprints.strath.ac.uk/id/eprint/32604

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