Estrone formate: a novel type of irreversible inhibitor of human steroid sulfatase

被引：17

作者：

Schreiner, EP ^{[1
]}

Billich, A ^{[1
]}

机构：

[1] GDC, Novartis Inst Biomed Res, A-1235 Vienna, Austria

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 19期

关键词：

steroid sulfatase; inactivator; estrone formate;

D O I：

10.1016/j.bmcl.2004.07.013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 IC50 of 0.42 muM 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. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4999 / 5002

页数：4

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