Fungal transformation of dydrogesterone and inhibitory effect of its metabolites on the respiratory burst in human neutrophils.
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).
Choudhary
M Iqbal
MI
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
Jalil
Saima
S
Musharraf
Syed Ghulam
SG
D001711:Biotransformation; D004394:Dydrogesterone / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D003904:Mitosporic Fungi / Q000378:metabolism*; D008968:Molecular Conformation; D009090:Mucorales / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011278:Pregnanes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011278:Pregnanes; D004394:Dydrogesterone