Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group
Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group
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DOI：
10.1016/j.bmc.2008.03.050
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Oyelere, Adegboyega K.
中科院分区：
文献类型：
--
作者：
Chen, Po C.;Patil, Vishal;Oyelere, Adegboyega K.
组蛋白去乙酰化酶（HDAC）抑制是最近临床验证的用于癌症治疗的治疗策略。迄今为止鉴定的小分子HDAC抑制剂落入三个不同的结构基序：锌结合基团（ZBG）、疏水连接体和识别帽基团。在这里，我们报告的适用性，1，2，3-三唑环作为表面识别帽基团连接部分辛二酰苯胺异羟肟酸样（SAHA样）HDAC抑制剂。使用“点击”化学（Huisgen环加成反应），合成了几种三唑连接的SAHA样异羟肟酸酯。构效关系表明，三唑基团的位置以及帽基团的性质显著影响该类化合物的体外HDAC抑制活性和细胞生长抑制活性。爱思唯尔有限公司出版
Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click'' chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure - activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds. Published by Elsevier Ltd.