Cinnamic acid esters as potent inhibitors of fungal 17beta-hydroxysteroid dehydrogenase--a model enzyme of the short-chain dehydrogenase/reductase superfamily.
We present the synthesis of a new family of nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase, designed from flavones and chalcones. Their inhibitory potential was screened on 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. In a series of cinnamates and related coumarin-3-carboxylates, a number of compounds proved to be potent inhibitors of both the oxidative and reductive reactions catalyzed by 17beta-HSDcl, with IC(50) values in the low micromolar range.
Gobec
Stanislav
S
Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. gobecs@ffa.uni-lj.si
Sova
Matej
M
Kristan
Katja
K
Rizner
Tea Lanisnik
TL
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D002934:Cinnamates / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D005658:Fungi / Q000187:drug effects / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D008954:Models, Biological
D002934:Cinnamates; D004791:Enzyme Inhibitors; C029010:cinnamic acid; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase