Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Mario Figueroa Saldivar, Adjunct Faculty (Creator)
Tyler Graf, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogues, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11'-deoxyverticillin A (6), and gliocladicillin A (7). The structures of compounds 1–7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1–7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC50 values ranging from 1.2 µM to 10 nM. Compounds 1–5 were examined for activity in the NF-?B assay, where compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally, compounds 1, 3, and 4 were tested for EGFR inhibition using an enzymatic assay, while compound 3 was examined against an overexpressing EGFR+ve cancer cell line.

Additional Information

Journal of Antibiotics, 2012, 65, pp 559-564
Language: English
Date: 2012
fungus, epipolythiodioxopiperazine alkaloids, cytotoxicity, NF-?B, EGFR

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