The microbial hydroxylation of levonorgestrel

Nat Prod Res. 2006 Oct;20(12):1074-81. doi: 10.1080/14786410500463411.

Abstract

The microbial transformation of levonorgestrel (1) by Cunningham elegans resulted in the formation of five hydroxylated metabolites, 13-ethyl-10beta, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one(2), 13-ethyl-6beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (3) 13-ethyl 6beta, 10beta, 17beta-trihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (4) 13-ethyl-15alpha-17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one (5) and 13-ethyl-11alpha, 17beta-dihydroxy-18,19-dinor-17alpha-pregn-4en-20-yn-3-one. The fermentation of one with Rhizopus stolonifer, Fusarium lini and Curvularia lunata afforded compound 2 as a major metabolise. These metabolites were structurally characterized on the basis of spectroScopic techniques. Metabolite 6 was identified as a new compound. Compounds 2 2 ad 5 displayed inhibitory activity against the acetylcholinesterase ( AChE, EC. 3.1.1.7) with IC50 values of 79.2 and 24.5 microM, respectively. The metabolites 2 and 5 also showed inhibitory activity against the butyryLcholinesterase ( BChE, E.C 3.1.1.8) with IC50 values ranging between 9.4 and 309.8 microM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / metabolism*
  • Cunninghamella / metabolism*
  • Fermentation
  • Hydroxylation
  • Inhibitory Concentration 50
  • Levonorgestrel / chemistry*
  • Levonorgestrel / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Structure
  • Norpregnanes / chemistry*
  • Norpregnanes / metabolism*
  • Spectrum Analysis

Substances

  • 13-ethyl-10beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one
  • Cholinesterase Inhibitors
  • Norpregnanes
  • Levonorgestrel
  • Butyrylcholinesterase