Author/Editor		Bacsa, Ildikó; Herman, Bianka Edina; Jójárt, Rebeka; Herman, Kevin Stefán; Wólfling, János; Schneider, Gyula; Tömböly, Csaba; Lanišnik-Rižner, Tea; Szécsi, Mihály; Mernyák, Erzsébet
Title		Synthesis and structure-activity relationships of 2- and/or 4-halogenated 13[beta]- and 13[alpha]-estrone derivatives as enzyme inhibitors of estrogen biosynthesis
Type		članek
Vol. and No.		Letnik 33, št. 1
Publication year		2018
Volume		str. 1271-1282
ISSN		1475-6366 - Journal of enzyme inhibition and medicinal chemistry
Language		eng
Abstract		Ring A halogenated 13[alpha], 13[beta], and 17-deoxy-13[alpha]-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[beta]-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[beta]-hydroxysteroid dehydrogenase 1 and competitive irreversible manner in the inhibition of the steroid sulfatase enzyme.
Keywords		estrogen biosynthesis enzyme inhibitors estrogen biosinteza encimski inhibitorji