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Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13?- and 13?-estrone derivatives as enzyme inhibitors of estrogen biosynthesis.

ABSTRACT: Ring A halogenated 13?-, 13?-, and 17-deoxy-13?-estrone derivatives were synthesised with N-halosuccinimides as electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17?-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory properties. Valuable structure-activity relationships were established from the comparison of the inhibitory data obtained. Kinetic experiments performed with selected compounds revealed competitive reversible inhibition mechanisms against 17?-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.

SUBMITTER: Bacsa I 

PROVIDER: S-EPMC6147116 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13β- and 13α-estrone derivatives as enzyme inhibitors of estrogen biosynthesis.

Bacsa Ildikó I   Herman Bianka Edina BE   Jójárt Rebeka R   Herman Kevin Stefán KS   Wölfling János J   Schneider Gyula G   Varga Mónika M   Tömböly Csaba C   Rižner Tea Lanišnik TL   Szécsi Mihály M   Mernyák Erzsébet E  

Journal of enzyme inhibition and medicinal chemistry 20181201 1

Ring A halogenated 13α-, 13β-, and 17-deoxy-13α-estrone derivatives were synthesised with N-halosuccinimides as electrophile triggers. Substitutions occurred at positions C-2 and/or C-4. The potential inhibitory action of the halogenated estrones on human aromatase, steroid sulfatase, or 17β-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Potent submicromolar or low micromolar inhibitors were identified with occasional dual or multiple inhibitory  ...[more]

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