Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.
Synthesis and Biological Evaluation of Novobiocin Core Analogues as Hsp90 Inhibitors.
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DOI：
10.1002/chem.201504955
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发表时间：
2016-05-10
期刊：
影响因子：
--
通讯作者：
Blagg BS
中科院分区：
文献类型：
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作者：
Byrd KM;Subramanian C;Sanchez J;Motiwala HF;Liu W;Cohen MS;Holzbeierlein J;Blagg BS
开发热休克蛋白90（Hsp 90）C-末端抑制剂已成为治疗癌症的一个令人兴奋的策略。以前的努力集中在天然产物新生霉素和香豆霉素的修饰上。此外，糖和酰胺部分的变化已被广泛研究，而香豆素核心的替代品却很少受到关注。在本文中，合成了24个核心，其中糖和酰胺部分之间的距离和角度不同。对多种癌细胞系表现出良好的抗增殖活性和Hsp 90抑制活性的化合物是将糖和酰胺部分以沿着180°的角度放置在7.7至12.1 μ m之间的化合物。
Development of Heat shock protein 90 (Hsp90) C-terminal inhibitors has emerged as an exciting strategy for the treatment of cancer. Previous efforts have focused on modifications to the natural products novobiocin and coumermycin. Moreover, variations in both the sugar and amide moieties have been extensively studied, whereas replacements for the coumarin core have received less attention. Herein, 24 cores were synthesized with varying distances and angles between the sugar and amide moieties. Compounds that exhibited good anti-proliferative activity against multiple cancer cell lines and Hsp90 inhibitory activity, were those that placed the sugar and amide moieties between 7.7 to 12.1 Å apart along with angles of 180°.