Comparative investigation of the in vitro inhibitory potencies of 13-epimeric estrones and D-secoestrones towards 17β-hydroxysteroid dehydrogenase type 1

Herman, BE [Herman, Bianka Edina (Elméleti orvostud...), author] First Department of Internal Medicine (USZ / ÁOK); Szabó, J [Szabó, Johanna (szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Bacsa, I [Bacsa, Ildikó (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Wölfling, J [Wölfling, János (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Schneider, G [Schneider, Gyula (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Bálint, M [Bálint, Mónika Enikő (Biokémia, Molekul...), author] Department of Biochemistry (ELTE / ELU FoS / Bio_I); Hetényi, C [Hetényi, Csaba (Farmakoinformatik...), author] MTA-ELTE Molecular Biophysics Research Group (ELTE / ELU FoS / Bio_I); Mernyák, E ✉ [Mernyák, Erzsébet (Szerves kémia), author] Department of Organic Chemistry (USZ / TTIK / KI); Szécsi, M ✉ [Szécsi, Mihály (Szteroidok analit...), author] First Department of Internal Medicine (USZ / ÁOK)

English Scientific Article (Journal Article)
  • SJR Scopus - Drug Discovery: Q2
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    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 IC50 value 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 IC50 value of 0.070 μM and is one of the most effective 17β-HSD1 inhibitors reported to date in the literature. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
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    2020-09-30 21:37