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

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  • A. Basilio, Merck, Spanien
  • M. Justice, Merck, USA
  • G. Harris, Merck, USA
  • G. Bills, Merck, Spanien
  • M de la Cruz, Merck, Spanien
  • M.T. Diez, Merck, Spanien
  • P. Hernandez, Merck, Spanien
  • P. Liberator, Merck, USA
  • J. Nielsen-Kahn, Merck, USA
  • F. Pelaez, Merck, USA
  • G. Platas, Merck, USA
  • D. Schmatz, Merck, USA
  • M. Shastry, Merck, USA
  • J.R. Tormo, Merck, Spanien
  • Gregers Rom Andersen
  • F. Vicente, Merck, Spanien
  • Molekylærbiologisk Institut
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.
OriginalsprogEngelsk
TidsskriftBioorg. Med. Chem.
Vol/bind14
Sider (fra-til)560-566
Antal sider7
StatusUdgivet - 2006

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