title: 17 alpha-alkyl- or 17 alpha-substituted benzyl-17 beta-estradiols: a new family of estrone-sulfatase inhibitors.
abstract: A series of 17 alpha-derivatives of 17 beta-estradiol was synthesized and tested for their ability to inhibit the estrone-sulfatase activity transforming estrone sulfate to estrone. A strong inhibitory activity was obtained when an alkyl side chain or a substituted benzyl was introduced at position 17 alpha of estradiol. The 17 alpha-(3'-bromobenzyl)-estradiol (26) and 17 alpha-(4'-t-butylbenzyl)-estradiol (30) were the most potent estrone-sulfatase inhibitors obtained in our study with IC50 values of 24 and 28 nM, respectively. They also represent a new family of estrone-sulfatase inhibitors. These compounds are about 300-fold more effective in interacting with the enzyme than the substrate estrone sulfate itself.
authors.affiliation: Medicinal Chemistry Division of LREM, CHUL Research Center, Laval University, Québec, QC, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Poirier
authors.forename: R P
authors.initials: RP
authors.lastname: Boivin
mesh_terms: D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D004958:Estradiol; D013429:Sulfatases; C020121:estrone sulfatase