Alpha-glucosidase and tyrosinase inhibitors from fungal hydroxylation of tibolone and hydroxytibolones.
Sixteen new and one known metabolites 4-20 were obtained by incubation of tibolone (1) and hydroxytibolones (2 and 3) with various fungi. Their structures were elucidated by means of a homo and heteronuclear 2D NMR and by HREI-MS techniques. The relative stereochemistry was deduced by 2D NOESY experiment. Metabolites of tibolone (1) exhibited significant inhibitory activities against alpha-glucosidase and tyrosinase enzymes. Hydroxylations at C-6, C-10, C-11, C-15 positions and alpha,beta-unsaturation at C-1/C-2, C-4/C-5 showed potent inhibitory activities against these enzymes.
Choudhary
M Iqbal
MI
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
Shah
S Adnan Ali
SA
Atta-ur-Rahman
Khan
Shamsun-Nahar
SN
Khan
Mahmud Tareq Hassan
MT
D001711:Biotransformation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D005285:Fermentation; D005658:Fungi / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D009652:Norpregnenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D009652:Norpregnenes; D014442:Monophenol Monooxygenase; C027385:tibolone