Novobiocin analogues with second-generation noviose surrogates

被引：29

作者：

Zhao, Huiping ^{[1
]}

Blagg, Brian S. J. ^{[1
]}

机构：

[1] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 02期

关键词：

Heat shock protein 90; Hsp90; inhibitors; Novobiocin analogues; Breast cancer; MANIFEST ANTIPROLIFERATIVE ACTIVITY; HSP90; INHIBITORS;

D O I：

10.1016/j.bmcl.2012.11.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hsp90 is a promising therapeutic target for the treatment of cancer. Novobiocin is the first Hsp90 C-terminal inhibitor ever identified and recent structure-activity relationship studies on the noviose sugar identified several commercially available amines as suitable surrogates. In an effort to further understand this region of the molecule, analogues containing various N'-amino substituents were prepared and evaluated against two breast cancer cell lines for determination of their efficacy. Compound 37j manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation at mid nano-molar concentrations. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：552 / 557

页数：6

共 23 条

[1] Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation [J].