N-Benzoyl anthranilic acid derivatives as selective inhibitors of aldo-keto reductase AKR1C3

被引：17

作者：

Sinreih, Masa ^{[2
]}

Sosic, Izidor ^{[1
]}

Beranic, Natasa ^{[2
]}

Turk, Samo ^{[1
]}

Adeniji, Adegoke O. ^{[3
]}

Penning, Trevor M. ^{[3
]}

Rizner, Tea Lanisnik ^{[2
]}

Gobec, Stanislav ^{[1
]}

机构：

[1] Univ Ljubljana, Fac Pharm, Ljubljana, Slovenia

[2] Univ Ljubljana, Fac Med, Inst Biochem, Ljubljana 61000, Slovenia

[3] Univ Penn, Perelman Sch Med, Ctr Excellence Environm Toxicol, Philadelphia, PA 19104 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 18期

关键词：

Anthranilic acid; AKR1C3; inhibitors; Anticancer agents; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTATE-CANCER; ENZYME; 17-BETA-HYDROXYSTEROID-DEHYDROGENASE; AGENTS; METABOLISM; EXPRESSION; ANALOGS;

D O I：

10.1016/j.bmcl.2012.07.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Human aldo-keto reductases AKR1C1-AKR1C3 are involved in the biosynthesis and inactivation of steroid hormones and prostaglandins and thus represent attractive targets for the development of new drugs. We synthesized a series of N-benzoyl anthranilic acid derivatives and tested their inhibitory activity on AKR1C enzymes. Our data show that these derivatives inhibit AKR1C1-AKR1C3 isoforms with low micromolar potency. In addition, five selective inhibitors of AKR1C3 were identified. The most promising inhibitors were compounds 10 and 13, with IC50 values of 0.31 mu M and 0.35 mu M for AKR1C3, respectively. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5948 / 5951

页数：4

共 20 条

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