Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products.
Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11beta-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11beta, 17alpha,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11beta, 17alpha, 21-trihydroxy-5alpha-pregnan-3, 20-dione (4) and 3beta, 11beta, 17alpha, 21-tetrahydroxy-5alpha-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 microM) and 4 (IC50 157 microM) have shown significant inhibitory activity against PEP.
H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan.
M Iqbal
MI
Choudhary
Sadia
S
Sultan
Muhammad
M
Yaqoob
S Ghulam
SG
Musharraf
Amsha
A
Yasin
Farzana
F
Shaheen
Atta-Ur-Rahman
D001711:Biotransformation; D004345:Drug Industry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005874:Gibberella / Q000201:enzymology*; D006854:Hydrocortisone / Q000378:metabolism* / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D006854:Hydrocortisone