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

A.H. Aly, A. Debbab, Ruangelie Edrada-Ebel, W.E.G. Muller, M.H.G. Kubbutat, V. Wray, Rainer Ebel, P. Proksch

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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.
Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalMycosphere, journal of fungal biology
Volume1
Publication statusPublished - 2010

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Keywords

  • cytotoxic activity
  • endophytic fungi
  • natural products
  • protein kinase

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