Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum

Lin Du, Andrew J. Robles, Jarrod B. King, Susan L. Mooberry, Robert H. Cichewicz

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20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1459-1466
Number of pages8
JournalJournal of Natural Products
Volume77
Issue number6
DOIs
Publication statusPublished - Jun 27 2014

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ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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