title: Phytoestrogens as inhibitors of fungal 17beta-hydroxysteroid dehydrogenase.
abstract: Different phytoestrogens were tested as inhibitors of 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl), a member of the short-chain dehydrogenase/reductase superfamily. Phytoestrogens inhibited the oxidation of 100 microM 17beta-hydroxyestra-4-en-3-one and the reduction of 100 microM estra-4-en-3,17-dione, the best substrate pair known. The best inhibitors of oxidation, with IC(50) below 1 microM, were flavones hydroxylated at positions 3, 5 and 7: 3-hydroxyflavone, 3,7-dihydroxyflavone, 5,7-dihydroxyflavone (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 IC(50) values between 1 and 5 microM. Docking the representative inhibitors chrysin and kaempferol into the active site of 17beta-HSDcl 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 17beta-HSD, are similar to the reported structural features of phytoestrogen inhibitors of human 17beta-HSD types 1 and 2.
authors.affiliation: Institute of Biochemistry, Medical Faculty, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Kristan
authors.forename: Katja
authors.initials: K
authors.lastname: Krajnc
authors.forename: Janez
authors.initials: J
authors.lastname: Konc
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Jure
authors.initials: J
authors.lastname: Stojan
authors.forename: Tea Lanisnik
authors.initials: TL
authors.lastname: Rizner
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000735:Androstenedione / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D001203:Ascomycota / Q000201:enzymology* / Q000235:genetics; D047309:Flavones / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D048789:Phytoestrogens / Q000494:pharmacology*; D028321:Plant Preparations; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D047072:Aromatase Inhibitors; D047309:Flavones; D048789:Phytoestrogens; D028321:Plant Preparations; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases