Publication: Cytotoxic metabolites from the endophytic fungus Penicillium chermesinum: Discovery of a cysteine-targeted Michael acceptor as a pharmacophore for fragment-based drug discovery, bioconjugation and click reactions
Issued Date
2015-08-11
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ISSN
20462069
Other identifier(s)
2-s2.0-84940398447
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Mahidol University
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SCOPUS
Bibliographic Citation
RSC Advances. Vol.5, No.86 (2015), 70595-70603
Suggested Citation
Cici Darsih, Vilailak Prachyawarakorn, Suthep Wiyakrutta, Chulabhorn Mahidol, Somsak Ruchirawat, Prasat Kittakoop Cytotoxic metabolites from the endophytic fungus Penicillium chermesinum: Discovery of a cysteine-targeted Michael acceptor as a pharmacophore for fragment-based drug discovery, bioconjugation and click reactions. RSC Advances. Vol.5, No.86 (2015), 70595-70603. doi:10.1039/c5ra13735g Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35696
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Title
Cytotoxic metabolites from the endophytic fungus Penicillium chermesinum: Discovery of a cysteine-targeted Michael acceptor as a pharmacophore for fragment-based drug discovery, bioconjugation and click reactions
Abstract
© The Royal Society of Chemistry 2015. Fungal metabolites (1-8) including known compounds, TMC-264 (1), PR-toxin (6) and a sesquiterpene (7), and new natural products 2-5 and 8, were isolated from the mangrove endophytic fungus Penicillium chermesinum. Compound 2 was a novel tetracyclic polyketide uniquely spiro-attached with a γ-lactone ring. Compounds 1 and 6 exhibited comparable cytotoxic activity to that of doxorubicin, and they selectively exhibited activity toward certain cancer cell lines. The cytotoxicity of 1 might be due to the β-chloro substituted α,β-unsaturated ketone functionality, which was reactive toward glutathione and peptides containing a thiol group. The polyketide 1 reacted with glutathione and peptides under physiological conditions, and its thiol-reactive pharmacophore is possibly applicable to the design of glutathione modulation agents, fragment-based drug discovery (for irreversible enzyme inhibitors), bioconjugation, and click reactions. Facile C-S bond formation in water (catalyst-free conditions) inspired by 1 could also be useful for green chemistry.
