A potent HDAC inhibitor, 1-alaninechlamydocin, from a Tolypocladium sp. induces G2/M cell cycle arrest and apoptosis in MIA PaCa-2 cells

Lin Du, April L. Risinger, Jarrod B. King, Douglas R. Powell, Robert H. Cichewicz

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The cyclic tetrapeptide 1-alaninechlamydocin was purified from a Great Lakes-derived fungal isolate identified as a Tolypocladium sp. Although the planar structure was previously described, a detailed analysis of its spectroscopic data and biological activity are reported here for the first time. Its absolute configuration was determined using a combination of spectroscopic (1H-1H ROESY, ECD, and X-ray diffraction) and chemical (Marfey's analysis) methods. 1-Alaninechlamydocin showed potent antiproliferative/cytotoxic activities in a human pancreatic cancer cell line (MIA PaCa-2) at low-nanomolar concentrations (GI50 5.3 nM, TGI 8.8 nM, LC50 22 nM). Further analysis revealed that 1-alaninechlamydocin induced G2/M cell cycle arrest and apoptosis. Similar to other cyclic epoxytetrapeptides, the inhibitory effects of 1-alaninechlamydocin are proposed to be produced primarily via inhibition of histone deacetylase (HDAC) activity.

Original languageEnglish (US)
Pages (from-to)1753-1757
Number of pages5
JournalJournal of Natural Products
Volume77
Issue number7
DOIs
Publication statusPublished - Jul 25 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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