Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils

Chem Biodivers. 2008 Feb;5(2):324-31. doi: 10.1002/cbdv.200890030.

Abstract

The biotransformation of the synthetic hormone dydrogesterone (1) by a number of fungal strains - including Cephalosporium aphidicola, Rhizopus stolonifer, Cunninghamella elegans, and Fusarium lini - afforded ten different metabolites, compounds 2-11. From a structural point of view, these transformations involved a combination of hydroxylation, oxidation, reduction, and/or epoxidation. The pregnane-based metabolites 10 and 11 are new compounds. All the known compounds were obtained for the first time from 1 by fungal transformation. The metabolites 3, 5, and 8 showed more-potent respiratory-burst inhibitory activity than the substrate 1 in a neutrophil-based cellular assay (Table 3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotransformation
  • Dydrogesterone / chemistry
  • Dydrogesterone / metabolism*
  • Humans
  • Mitosporic Fungi / metabolism*
  • Molecular Conformation
  • Mucorales / metabolism*
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Pregnanes / chemistry
  • Pregnanes / metabolism*
  • Pregnanes / pharmacology
  • Respiratory Burst / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Pregnanes
  • Dydrogesterone