Estradiol dimers as a new class of steroid sulfatase reversible inhibitors

被引：14

作者：

Fournier, Diane

Poirier, Donald ^{[1
]}

机构：

[1] CHUQ CHUL Res Ctr, Div Med Chem, Oncol & Mol Endocrinol Lab, Quebec City, PQ G1V 4G2, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 03期

基金：

加拿大健康研究院;

关键词：

Sulfatase; Steroid; Inhibitor; Dimer; Enzyme; Cancer; ESTRONE SULFATASE; BREAST-CANCER; MODULATORS; ENZYMES; TISSUE;

D O I：

10.1016/j.bmcl.2008.12.047

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of estradiol dimers was synthesized or selected from compounds available in our laboratory and tested for inhibition against steroid sulfatase. Dimers linked by their C17 position, compounds 7 and 8, showed inhibitory potency similar (56% and 54% at 1 mu M) to that of our best previously reported reversible inhibitor EM-690 (62% at 1 mu M). Docking experiment seems to indicate that C17-C17 dimers bind in a similar way to EM-690 whereas C16-O3 and C16-C16 dimers bind in an upside-down position. (c) 2008 Elsevier Ltd. All rights reserved.

引用

收藏

页码：693 / 696

页数：4

相关论文

共 30 条

[1] Review of estrone sulfatase and its inhibitors - An important new target against hormone dependent breast cancer [J].

Ahmed, S ;

Owen, CP ;

James, K ;

Sampson, L ;

Patel, CK .

CURRENT MEDICINAL CHEMISTRY, 2002, 9 (02) :263-273

[2] Boronic acids as inhibitors of steroid sulfatase [J].

Ahmed, Vanessa ;

Liu, Yong ;

Silvestro, Cassandra ;

Taylor, Scott D. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2006, 14 (24) :8564-8573

[3] Structure-activity relationships of 17α-derivatives of estradiol as inhibitors of steroid sulfatase [J].

Boivin, RP ;

Luu-The, V ;

Lachance, R ;

Labrie, F ;

Poirier, D .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (23) :4465-4478

[4]

*CAN CANC SOC NAT, 2008, CAN CANC STAT 2008

[5] Potent inhibition of steroid sulfatase activity by 3-O-sulfamate 17α-benzyl(or 4′-tert-butylbenzyl)estra-1,3,5(10)-trienes:: Combination of two substituents at positions C3 and C17α of estradiol [J].

Ciobanu, LC ;

Boivin, RP ;

Luu-The, V ;

Labrie, F ;

Poirier, D .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (12) :2280-2286

[6] Synthesis of libraries of 16β-aminopropyl estradiol derivatives for targeting two key steroidogenic enzymes [J].

Ciobanu, Liviu C. ;

Poirier, Donald .

CHEMMEDCHEM, 2006, 1 (11) :1249-1259

[7] Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: A systematic review [J].

Eisen, Andrea ;

Trudeau, Maureen ;

Shelley, Wendy ;

Messersmith, Hans ;

Pritchard, Kathleen I. .

CANCER TREATMENT REVIEWS, 2008, 34 (02) :157-174

[8] Human sulfatases: A structural perspective to catalysis [J].

Ghosh, D. .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2007, 64 (15) :2013-2022

[9] Three-dimensional structures of sulfatases [J].

Ghosh, D .

PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS, 2005, 400 :273-+

[10] Sulfatases: Structure, mechanism, biological activity, inhibition, and synthetic utility [J].

Hanson, SR ;

Best, MD ;

Wong, CH .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (43) :5736-5763