The microbial hydroxylation of levonorgestrel.
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.
Choudhary
Muhammad Iqbal
MI
HEJ Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan. hej@ctber.net.pk
Atif
Muhammad
M
Nawaz
Sarfraz A
SA
Fatmi
Muhammad Qaiser
MQ
Atta-Ur-Rahman
D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D020093:Cunninghamella / Q000378:metabolism*; D005285:Fermentation; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D016912:Levonorgestrel / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009650:Norpregnanes / Q000737:chemistry* / Q000378:metabolism*; D013057:Spectrum Analysis
C518342:13-ethyl-10beta,17beta-dihydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one; D002800:Cholinesterase Inhibitors; D009650:Norpregnanes; D016912:Levonorgestrel; D002091:Butyrylcholinesterase