Author/Editor     Kristan, Katja; Krajnc, Katja; Konc, Janez; Gobec, Stanislav; Stojan, Jure; Lanišnik-Rižner, Tea
Title     Phytoestrogens as inibitors of fungal 17beta-hydroxysteroid dehydrogenase
Type     članek
Source     Steroids
Vol. and No.     Letnik 70
Publication year     2005
Volume     str. 626-35
Language     eng
Abstract     Different phytoestrogens were tested as inhibitors of 17B-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17BHSDcI), a member of the short-chain dehydrogenase/reductase superfamily. Phytoestrogens inhibited the oxidation of 100 uM 17B-hydroxyestra-4-en-3-one and the reduction of 100 uM estra-4-en-3,17-dione, the best substrate pair known. The best inhibitors of oxidation, with IC50 below 1 uM, were flavones hydroxylated at positions 3, 5 and 7: 3-hydroxyflavone, 3,7-dihydroxyftavone, 5,7-dihydroxyftavone (chrysin) and 5-hydroxyflavone, together with 5-methoxyflavone. The best inhibitors of reduction were less potent; 3-hydroxyflavone, 5-methoxyflavone, coumestrol, 3,5,7,4'-tetrahydroxyflavone (kaempferol) and 5-hydroxyflavone, all had IC50 values between 1 and 5 uM. Docking the representative inhibitors chrysin and kaempferol into the active site of 17B-HSDcI revealed the possible binding mode, in which they are sandwiched between the nicotinamide moiety and Tyr212. The structural features of phytoestrogens, inhibitors of both oxidation and reduction catalyzed by the fungal 17B-HSD, are similar to the reported structural features of phytoestrogen inhibitors of human 17B-HSD types 1 and 2.
Descriptors     ASCOMYCETES
17-HYDROXYSTEROID DEHYDROGENASES
ENZYME INHIBITORS
PLANT EXTRACTS
ESTROGENS
FLAVONES
BINDING SITES