The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity.
The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity.
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DOI：
10.1021/jo801312r
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发表时间：
2008-11-21
影响因子：
3.6
通讯作者：
Blagg, Brian S. J.
中科院分区：
文献类型：
--
作者：
Donnelly, Alison C.;Mays, Jared R.;Burlison, Joseph A.;Nelson, John T.;Vielhauer, George;Holzbeierlein, Jeffrey;Blagg, Brian S. J.
新生霉素是一种已知的DNA促旋酶抑制剂，在乳腺癌细胞（SkBr 3）中，它与位于Hsp 90 C-末端的核苷酸结合位点结合，并在约700 μM浓度下诱导Hsp 90依赖性客户蛋白降解。虽然新生霉素的许多类似物已被合成，但直到最近才证明单体物质可对各种癌细胞系表现出抗增殖活性。为了进一步完善香豆素核心的基本元素，合成了一系列修饰的香豆素衍生物，并进行了评价，以阐明新生霉素作为抗癌剂的构效关系。从这些研究中获得的结果产生了新生霉素类似物，其对几种癌细胞系表现出低微摩尔活性。
Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at ~700 μM in breast cancer cells (SkBr3). Although many analogues of novobiocin have been synthesized, it was only recently demonstrated that monomeric species can exhibit anti-proliferative activity against various cancer cell lines. To further refine the essential elements of the coumarin core, a series of modified coumarin derivatives was synthesized and evaluated for elucidation of structure–activity relationships for novobiocin as an anti-cancer agent. Results obtained from these studies have produced novobiocin analogues that manifest low micromolar activity against several cancer cell lines.
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影响因子：
15
作者：
Klarmann, E
通讯作者：
Klarmann, E
影响因子：
50.3
作者：
Isaacs, JS;Xu, WP;Neckers, L
通讯作者：
Neckers, L
影响因子：
2.9
作者：
ALI, JA;JACKSON, AP;MAXWELL, A
通讯作者：
MAXWELL, A
影响因子：
4
作者：
AKIYAMA, T;TAKESUE, Y;OZAKI, S
通讯作者：
OZAKI, S
影响因子：
7.3
作者：
Das, Jagabandhu;Chen, Ping;Barrish, Joel C.
通讯作者：
Barrish, Joel C.