Cinnamates and cinnamamides inhibit fungal 17beta-hydroxysteroid dehydrogenase.
The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) have important roles in the regulation of steroid hormone actions through their catalysis of the oxidation or reduction of estrogens and androgens at position 17. Dysfunctions of the human 17beta-HSDs have been associated with reproduction disorders, neuronal diseases and the development of hormone-dependent forms of cancers. Therefore, these enzymes represent interesting targets for the development of new drugs. Here we present a series of new cinnamic acid esters and amides that inhibit the oxidative and reductive reaction catalyzed by 17beta-HSD from the fungus Cochliobolus lunatus, a model enzyme of the short-chain dehydrogenase/reductase superfamily. We found that esters of unsubstituted cinnamic acid were better inhibitors than esters of 3,4,5-trimethoxycinnamic acid. Cinnamates were also more potent inhibitors than structurally related cinnamamides. The compounds presented in this paper are potential leads for the development of inhibitors of human 17beta-HSD isoforms, which may prove to have different therapeutic applications.
Kristan
Katja
K
Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
Starcević
Stefan
S
Brunskole
Mojca
M
Rizner
Tea Lanisnik
TL
Gobec
Stanislav
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D001203:Ascomycota / Q000201:enzymology; D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50
D002934:Cinnamates; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; C411088:cinnamamide