Cytotoxic Dimeric Epipolythiodiketopiperazines fromthe Ascomycetous Fungus Preussia typharum

摘要

Two new dimeric epipolythiodiketopiperazines, preussiadins A (>1) and B (>2), together with two known diastereomers, leptosins C (>6) and A (>7), were obtained from the mycelia of a Preussia typharum isolate. The structures of the new compounds were established by spectroscopic methods, and the absolute configurations of >1 and >2 were assigned by chemical transformations and comparisons of quantum chemical ECD and VCD calculations to experimental data. Compound >1 exhibited potent cytotoxic activity in the NCI-60 cell line panel with an average LC50 value of 251 nM. Further studies demonstrated that >1 circumvents P-glycoprotein-mediated drug resistance, yet had no significant antitumor activity in a xenograft UACC-62 melanoma model.