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Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

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 analogs, 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 mu M to 10 nM. Compounds 1-5 were examined for activity in the NF-kappa 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. The Journal of Antibiotics (2012) 65, 559-564; doi: 10.1038/ja.2012.69; published online 12 September 2012


Figueroa, M., Graf, TN., Ayers, S., Adcock, AF., Kroll, DJ., Yang, J., ... Oberlies, NH. (2012). Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae. Journal of Antibiotics, 65(11), 559-564. https://doi.org/10.1038/ja.2012.69

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