New inhibitors of fungal 17beta-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold.
The synthesis and activity of a new series of non-steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17beta-HSDcl activity, with IC50 values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17beta-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases.
Zivec
Matej
M
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia.
Sova
Matej
M
Brunskole
Mojca
M
Lenarsic
Roman
R
Rizner
Tea Lanisnik
TL
Gobec
Stanislav
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D001203:Ascomycota / Q000201:enzymology*; D001569:Benzodiazepines / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared
D004791:Enzyme Inhibitors; D001569:Benzodiazepines; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase