Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines

被引：118

作者：

Burlison, Joseph A. ^{[1
]}

Avila, Christopher ^{[2
]}

Vielhauer, George ^{[2
]}

Lubbers, Donna J. ^{[1
]}

Holzbeierlein, Jeffrey ^{[2
]}

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

机构：

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

[2] Univ Kansas, Med Ctr, Dept Urol, Kansas City, KS 66160 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2008年 / 73卷 / 06期

关键词：

D O I：

10.1021/jo702191a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Recent studies have shown that the DNA gyrase inhibitor, novobiocin, binds to a previously unrecognized ATP-binding site located at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at similar to 700 mu M. As a result of these studies, several analogues of the coumarin family of antibiotics have been reported and shown to exhibit increased Hsp90 inhibitory activity; however, the monomeric species lacked the ability to manifest anti-proliferative activity against cancer cell lines at concentrations tested. In an effort to develop more efficacious compounds that produce growth inhibitory activity against cancer cell lines, structure-activity relationships; were investigated surrounding the prenylated benzamide side chain of the natural product. Results obtained from these studies have produced the first novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines.

引用

页码：2130 / 2137

页数：8

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