Amide derivatives of ethacrynic acid: Synthesis and evaluation as antagonists of Wnt/β-catenin signaling and CLL cell survival

被引：32

作者：

Jin, Guangyi ^{[1
]}

Lu, Desheng ^{[1
]}

Yao, Shiyin ^{[1
]}

Wu, Christina C. N. ^{[1
]}

Liu, Jerry X. ^{[1
]}

Carson, Dennis A. ^{[1
]}

Cottam, Howard B. ^{[1
]}

机构：

[1] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

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

基金：

美国国家卫生研究院;

关键词：

Chronic lymphocytic leukemia; Wnt/beta-catenin signaling; Ethacrynic acid amides; Lef-1; CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER; PATHWAY; INHIBITION; MUTATION;

D O I：

10.1016/j.bmcl.2008.12.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amides of ethacrynic acid was prepared and evaluated for their ability to inhibit Wnt signaling and decrease the survival of CLL cells. Several of the most potent derivatives were active in the low micromolar range. Reduction of the alpha,beta-unsaturated carbon-carbon double bond of EA abrogated both the inhibition of Wnt signaling as well as the decrease in CLL survival. Preliminary mechanism of action studies suggest that these derivatives covalently modify sulfhydryl groups present on transcription factors important for Wnt/beta-catenin signaling. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：606 / 609

页数：4

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