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The discovery of moriniafungin, a novel sordarin derivative produced by Morinia pestalozzioides

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  • A. Basilio, Merck, Spain
  • M. Justice, Merck, United States
  • G. Harris, Merck, United States
  • G. Bills, Merck, Spain
  • M de la Cruz, Merck, Spain
  • M.T. Diez, Merck, Spain
  • P. Hernandez, Merck, Spain
  • P. Liberator, Merck, United States
  • J. Nielsen-Kahn, Merck, United States
  • F. Pelaez, Merck, United States
  • G. Platas, Merck, United States
  • D. Schmatz, Merck, United States
  • M. Shastry, Merck, United States
  • J.R. Tormo, Merck, Spain
  • Gregers Rom Andersen
  • F. Vicente, Merck, Spain
  • Department of Molecular Biology
A novel sordarin derivative, moriniafungin (1), containing a 2-hydroxysebacic acid residue linked to C-3′ of the sordarose residue of sordarin through a 1,3-dioxolan-4-one ring was isolated from the fungus Morinia pestalozzioides. Isolation of moriniafungin employed a highly specific bioassay consisting of a panel of Saccharomyces cerevisiae strains containing chimeric eEF2 for Candida glabrata, Candida krusei, Candida lusitaniae, Crytpococcus neoformans, and Aspergillus fumigatus as well as wild type and human eEF2. Moriniafungin exhibited an MIC of 6 μg/mL versus Candida albicans and IC50's ranging from 0.9 to 70 μg/mL against a panel of clinically relevant Candida strains. Moriniafungin was shown to inhibit in vitro translation in the chimeric S. cerevisae strains at levels consistent with the observed IC50. Moriniafungin has the broadest antifungal spectrum and most potent activity of any natural sordarin analog identified to date.
Original languageEnglish
JournalBioorg. Med. Chem.
Volume14
Pages (from-to)560-566
Number of pages7
Publication statusPublished - 2006

    Research areas

  • drug, fungicide, translation

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