title: Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum.
abstract: 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.
authors.affiliation: Natural Products Discovery Group, ‡Institute for Natural Products Applications and Research Technologies, and §Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, 101 Stephenson Parkway, University of Oklahoma , Norman, Oklahoma 73019-5251, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Robles
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: King
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008545:Melanoma / Q000473:pathology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010879:Piperazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D010879:Piperazines; C555444:epipolythiodiketopiperazine; C000591083:preussiadin A; C000591084:preussiadin B