title: Synthesis of A-ring halogenated 13α-estrone derivatives as potential 17β-HSD1 inhibitors.
abstract: 13α-Estrone and its 3-methyl or benzyl ether were halogenated in ring A with N-bromo- or N-iodosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin as electrophile triggers. The chemo- and regioselectivities of the reactions depended greatly on the nature of the substituent on C-3. Bromination of the ethers led to 2- and 4-regioisomers. Bis-halogenation occurred only in the case of the phenolic derivative. Iodination and bromination resulted in similar products, except that the 3-benzyl ether could not be iodinated under the applied conditions. The potential inhibitory action of the new halogenated 13α-estrones on human 17β-hydroxysteroid dehydrogenase 1 activity was investigated via in vitro radiosubstrate incubation. Some compounds proved to be effective inhibitors, with IC50 values in the submicromolar range.
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
authors.forename: Ildikó
authors.initials: I
authors.lastname: Bacsa
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
authors.forename: Rebeka
authors.initials: R
authors.lastname: Jójárt
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
authors.forename: Gyula
authors.initials: G
authors.lastname: Schneider
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Wölfling
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Maróti
authors.affiliation: 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary.
authors.forename: Bianka Edina
authors.initials: BE
authors.lastname: Herman
authors.affiliation: 1st Department of Medicine, University of Szeged, Korányi fasor 8-10, H-6720 Szeged, Hungary. Electronic address: szecsi.mihaly@med.u-szeged.hu.
authors.forename: Mihály
authors.initials: M
authors.lastname: Szécsi
authors.affiliation: Department of Organic Chemistry, University of Szeged, Dóm tér 8., H-6720 Szeged, Hungary. Electronic address: bobe@chem.u-szeged.hu.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Mernyák
mesh_terms: 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* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D004970:Estrone; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human
keywords: 13α-Estrone; 17β-HSD1 inhibition; Chemoselectivity; Electrophilic halogenation; Regioselectivity