Schreiner, Erwin and Billich, Andreas (2004) Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase. Bioorganic & Medicinal Chemistry Letters, 14 (19). pp. 4999-5002. ISSN 0960-894X

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2004.07.013
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Steroid sulfatase; Inactivator; Estrone formate
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2004.07.013
Date Deposited:	14 Dec 2009 13:55
Last Modified:	31 Jan 2013 01:08
URI:	https://oak.novartis.com/id/eprint/732