Bioactive metabolites from the endophytic fungus stemphylium globuliferum isolated from mentha pulegium

Adbessamad Debbab, Amal H. Aly, RuAngelie Edrada-Ebel, Victor Wray, Werner E.G. Muller, Frank Totzke, Ute Zirrgiebel, Christoph Schachtele, Michael H.G. Kubbutat, Wenhan Lin, Mahjouba Mosaddak, Adbelhak Hakikj, Peter Proksch, Rainer Ebel

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)

Abstract

The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts of the fungus, which was grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer alterporriol H (5), altersolanol K (11), altersolanol L (12), stemphypyrone (13), and the known compounds 6-O-methylalaternin (1), macrosporin (2), altersolanol A (3), alterporriol E (6), alterporriol D (7), alterporriol A (8), alterporriol B (9), and altersolanol J (10). The structures were determined on the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. Among the alterporriol-type anthranoid dimers, the mixture of alterporriols G and H (4/5) exhibited considerable cytotoxicity against L5178Y cells with an EC50 value of 2.7 μg/mL, whereas the other congeners showed only modest activity. The compounds were also tested for kinase inhibitory activity in an assay involving 24 different kinases. Compounds 1, 2, 3, and the mixture of 4 and 5 were the most potent inhibitors, displaying EC50 values between 0.64 and 1.4 μg/mL toward individual kinases.
Original languageEnglish
Pages (from-to)626-631
Number of pages5
JournalJournal of Natural Products
Volume72
Issue number4
DOIs
Publication statusPublished - Mar 2009

Keywords

  • bioactive metabolites
  • endophytic fungus
  • stemphylium globuliferum
  • mentha pulegium
  • pharmacology

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