Synthesis of substituted 15β-alkoxy estrone derivatives and their cofactor-dependent inhibitory effect on 17β-HSD1

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a key enzyme in the biosynthesis of 17β-estradiol. Novel estrone-based compounds bearing various 15β-oxa-linked substituents and hydroxy, methoxy, benzyloxy, and sulfamate groups in position C3 as potential 17β-HSD1 inhibitors have been synthesiz...

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Veröffentlicht in:	Journal of enzyme inhibition and medicinal chemistry 2019-01, Vol.34 (1), p.1271-1286
Hauptverfasser:	Herman, Bianka Edina, Kiss, Anita, Wölfling, János, Mernyák, Erzsébet, Szécsi, Mihály, Schneider, Gyula
Format:	Artikel
Sprache:	eng
Schlagworte:	17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors 17-Hydroxysteroid Dehydrogenases - metabolism 17β-HSD1 Dose-Response Relationship, Drug Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology estrogen biosynthesis Estrone - chemical synthesis Estrone - chemistry Estrone - pharmacology Humans Michael addition Molecular Conformation NADPH and NADH Research Paper Structure-Activity Relationship substituted 15β-alkoxy-estrone derivatives
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Zusammenfassung:	17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a key enzyme in the biosynthesis of 17β-estradiol. Novel estrone-based compounds bearing various 15β-oxa-linked substituents and hydroxy, methoxy, benzyloxy, and sulfamate groups in position C3 as potential 17β-HSD1 inhibitors have been synthesized. In addition, in vitro inhibitory potentials measured in the presence of excess amount of NADPH or NADH were investigated. We observed substantial inhibitory potentials for several derivatives (IC 50
ISSN:	1475-6366 1475-6374
DOI:	10.1080/14756366.2019.1634064