title: Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase.
abstract: A series of estrone conjugates of the type estrone-3-O-C(O,S)-X have been prepared and evaluated for inhibition of human steroid sulfatase (STS). Among the carbamate (6), thiocarbamate (8), cyanate (7), formate (9), and acetate (10) analogs of estrone, only 9 was found to inhibit STS in a time- and concentration-dependent manner. With an IC(50) of 0.42 microM 9 is the first potent inactivator of STS which does not feature the sulfamate group. Furthermore a formate-type inhibitor featuring a benzoxazole moiety in place of the steroid skeleton (14) was prepared, suggesting a general principle of inactivation by the formate group. As the mode of action we propose an immediate transfer of the formyl moiety to a nucleophilic residue in the active site of STS.
authors.affiliation: Novartis Institutes for BioMedical Research GDC, Brunner Strasse 59, A-1235 Vienna, Austria. erwin.schreiner@pharma.novartis.com
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Schreiner
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004970:Estrone / Q000494:pharmacology*; D005561:Formates / Q000494:pharmacology*; D006801:Humans; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D005561:Formates; D004970:Estrone; D043266:Steryl-Sulfatase