Abstract
Macrocyclic trichothecenes (MTs), which have potent cytotoxicity, have been isolated from many different fungal species. These compounds were evaluated clinically by the US National Cancer Institute in the 1970s and 1980s. However, they have yet to be advanced into viable drugs because of severe side effects. Our team is investigating a diverse library of filamentous fungi for new anticancer leads. To avoid reisolating MTs through bioactivity-directed fractionation studies, a protocol for their facile dereplication was developed. The method uses readily available photodiode array detectors to identify one of two types of characteristic UV spectra for these compounds. In addition, diagnostic signals can be observed in the 1H-NMR spectra, particularly for the epoxide and conjugated diene moieties, even at the level of a crude extract. Using these techniques in a complementary manner, MTs can be dereplicated rapidly.
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Acknowledgements
This research was supported by P01 CA125066 from the National Cancer Institute/National Institutes of Health, Bethesda, MD, USA. The Golden LEAF Foundation (Rocky Mount, NC, USA) provided partial support to DJK. Mycology technical support was provided by Blaise Darveaux and Maurica Lawrence. We thank Drs AD Kinghorn and DS Ayers for helpful discussions.
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Sy-Cordero, A., Graf, T., Wani, M. et al. Dereplication of macrocyclic trichothecenes from extracts of filamentous fungi through UV and NMR profiles. J Antibiot 63, 539–544 (2010). https://doi.org/10.1038/ja.2010.77
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DOI: https://doi.org/10.1038/ja.2010.77
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