Cargando…

Cytotoxic Dimeric Epipolythiodiketopiperazines from the Ascomycetous Fungus Preussia typharum

[Image: see text] 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...

Descripción completa

Detalles Bibliográficos
Autores principales: Du, Lin, Robles, Andrew J., King, Jarrod B., Mooberry, Susan L., Cichewicz, Robert H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society and American Society of Pharmacognosy 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073660/
https://www.ncbi.nlm.nih.gov/pubmed/24893224
http://dx.doi.org/10.1021/np5002253
Descripción
Sumario:[Image: see text] 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 LC(50) 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.