title: Comparative investigation of the in vitro inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1.
abstract: The inhibitory effects of 13-epimeric estrones, D-secooxime and D-secoalcohol estrone compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated. The transformation of estrone to 17β-estradiol was studied by an in vitro radiosubstrate incubation method. 13α-Estrone inhibited the enzyme activity effectively with an IC50value of 1.2 μM, which indicates that enzyme affinity is similar to that of the natural estrone substrate. The 13β derivatives and the compounds bearing a 3-hydroxy group generally exerted stronger inhibition than the 13α and 3-ether counterparts. The 3-hydroxy-13β-D-secoalcohol and the 3-hydroxy-13α-D-secooxime displayed an outstanding cofactor dependence, i.e. more efficient inhibition in the presence of NADH than NADPH. The 3-hydroxy-13β-D-secooxime has an IC50value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature.
authors.affiliation: a 1st Department of Medicine, University of Szeged , Szeged , Hungary.
authors.forename: Bianka Edina
authors.initials: BE
authors.lastname: Herman
authors.affiliation: b Department of Organic Chemistry , University of Szeged , Szeged , Hungary.
authors.forename: Johanna
authors.initials: J
authors.lastname: Szabó
authors.affiliation: b Department of Organic Chemistry , University of Szeged , Szeged , Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Bacsa
authors.affiliation: b Department of Organic Chemistry , University of Szeged , Szeged , Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.affiliation: b Department of Organic Chemistry , University of Szeged , Szeged , Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.affiliation: c Department of Biochemistry , Eötvös Loránd University , Budapest , Hungary , and.
authors.forename: Mónika
authors.initials: M
authors.lastname: Bálint
authors.affiliation: d MTA-ELTE Molecular Biophysics Research Group, Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Hetényi
authors.affiliation: b Department of Organic Chemistry , University of Szeged , Szeged , Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
authors.affiliation: a 1st Department of Medicine, University of Szeged , Szeged , Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Szécsi
mesh_terms: D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004970:Estrone; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human
keywords: 13α-estrone; 17β-HSD1 inhibition; D-secoestrone; NADH; NADPH