Diterpene glycosides and polyketides from Xylotumulus gibbisporus

J Nat Prod. 2014 Apr 25;77(4):751-7. doi: 10.1021/np400523k. Epub 2014 Mar 5.

Abstract

Four new tetracyclic diterpene glycosides, namely, sordarins C-F (1-4), and three new γ-lactone polyketides, namely, xylogiblactones A-C (5-7), along with sordarin were isolated from the ethyl acetate extracts of the fermented broths of Xylotumulus gibbisporus YMJ863. The structures of 1-7 were elucidated on the basis of spectroscopic data analyses. The configurations of 1-4 were deduced by NOESY, molecular modeling, and comparison with the literature. The relative configurations of 5-7 were deduced by X-ray crystallographic analysis of 5. Compounds 1-5 and sordarin were evaluated in an antifungal assay using Candida albicans ATCC 18804, C. albicans ATCC MYA-2876, and Saccharomyces cerevisiae ATCC 2345, and only sordarin exhibited significant antifungal activities against these fungal strains, with MIC values of 64.0, 32.0, and 32.0 μg/mL, respectively. The effect of compounds 1-7 and sordarin on the inhibition of NO production in lipopolysaccharide-activated murine macrophages was also evaluated. Compounds 2 and sordarin inhibited NO production with IC50 values of 327.2±46.6 and 157.1±24.1 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / isolation & purification*
  • Antifungal Agents / pharmacology
  • Candida albicans / drug effects
  • Crystallography, X-Ray
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology
  • Glycosides / chemistry
  • Glycosides / isolation & purification*
  • Glycosides / pharmacology
  • Hawaii
  • Indenes / chemistry
  • Indenes / pharmacology*
  • Inhibitory Concentration 50
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Conformation
  • Molecular Structure
  • Nitric Oxide / biosynthesis
  • Nuclear Magnetic Resonance, Biomolecular
  • Polyketides / chemistry
  • Polyketides / isolation & purification*
  • Polyketides / pharmacology
  • Saccharomyces cerevisiae / drug effects
  • Xylariales / chemistry*

Substances

  • Antifungal Agents
  • Diterpenes
  • Glycosides
  • Indenes
  • Lipopolysaccharides
  • Polyketides
  • sordarin
  • Nitric Oxide