title: Chemical synthesis and evaluation of 17α-alkylated derivatives of estradiol as inhibitors of steroid sulfatase.
abstract: Steroid sulfatase (STS) controls the levels of 3-hydroxysteroids available from circulating steroid sulfates in several normal and malignant tissues. This and the known involvement of active estrogens and androgens in diseases such as breast and prostate cancers thus make STS an interesting therapeutic target. Here we describe the chemical synthesis and characterization of an extended series of 17α-derivatives of estradiol (E2) using different strategies. A variant of the samarium-Barbier reaction with stoichiometric samarium metal and catalytic Kagan reagent formation was used for introducing low reactive benzyl substrates in position 17 of estrone (E1) whereas heterocyclic substrates were metalated and reacted with either the carbonyl or the 17-oxirane of E1. In vitro evaluation of the inhibitory potency of the new compounds against STS identified new inhibitors and allowed a more complete structure-activity relationship study of this family of 17α-derivatives of E2.
authors.affiliation: CHUQ-CHUL Research Center (Laboratory of Medicinal Chemistry, Endocrinology and Genomic Unit and Laval University, Faculty of Medicine, Quebec G1V 4G2, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Fournier
authors.forename: Donald
authors.initials: D
authors.lastname: Poirier
mesh_terms: D000478:Alkylation; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D004958:Estradiol; D043266:Steryl-Sulfatase