Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2.
Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2.
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DOI：
10.1016/j.bmcl.2019.06.059
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发表时间：
2019-06
影响因子：
2.7
通讯作者：
Yu Yu-Yu;Dongzhi Ran;junhao jiang;Tao Pan;Yanrong Dan;Q. Tang;Wei Li;Lin Zhang;Linling Gan;Zongjie Gan
中科院分区：
文献类型：
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作者：
Yu Yu-Yu;Dongzhi Ran;junhao jiang;Tao Pan;Yanrong Dan;Q. Tang;Wei Li;Lin Zhang;Linling Gan;Zongjie Gan
HDAC和CDK抑制剂已被证明在抑制癌细胞增殖和诱导细胞凋亡方面具有协同作用。在这项工作中，我们将HDAC和CDK抑制剂的药效团整合到一个分子中，设计并合成了一系列作为HDAC/CDK双重抑制剂的嘌呤衍生物。先导化合物6d显示出良好的HDAC1和CDK2抑制活性，IC50值分别为5.8nM和56 nM，对几种癌细胞株具有诱人的体外抑制活性。这项工作可能会导致发现一种新型的支架和潜在的HDAC/CDK双重抑制剂。
HDAC and CDK inhibitors have been demonstrated to be synergistically in suppressing cancer cell proliferation and inducing apoptosis. In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one molecule to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. The lead compound6d, showing good HDAC1 and CDK2 inhibitory activity with IC50values of 5.8 and 56 nM, respectively, exhibited attractive potency against several cancer cell lines in vitro. This work may lead to the discovery of a novel scaffold and potential dual HDAC/CDK inhibitors.