Cici DarsihVilailak PrachyawarakornSuthep WiyakruttaChulabhorn MahidolSomsak RuchirawatPrasat KittakoopChemical Biology ProgramChulabhorn Research InstituteMahidol UniversitySouth Carolina Commission on Higher Education2018-11-232018-11-232015-08-11RSC Advances. Vol.5, No.86 (2015), 70595-70603204620692-s2.0-84940398447https://repository.li.mahidol.ac.th/handle/20.500.14594/35696© 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.Mahidol UniversityChemical EngineeringChemistryArticleSCOPUS10.1039/c5ra13735g