Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro.
Synthesis of 6-(het) ary Xylocydine analogues and evaluating their inhibitory activities of CDK1 and CDK2 in vitro.
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DOI：
10.1016/j.bmc.2011.10.003
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发表时间：
2011-12
影响因子：
3.5
通讯作者：
Chuan Xiao;Chao Sun;Weiwei Han;Fengguang Pan;Zhu Dan;Y. Li;Zhi-guang Song;Ying-hua Jin
中科院分区：
文献类型：
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作者：
Chuan Xiao;Chao Sun;Weiwei Han;Fengguang Pan;Zhu Dan;Y. Li;Zhi-guang Song;Ying-hua Jin
合成了一系列6位含芳基和杂芳基的嘌呤核苷类似物，并通过体外CDK 1/Cyclin B1和CDK 2/Cyclin A2激酶活性测定法评价了它们的生物活性。在所合成的化合物中，三个Xylocydine衍生物3 h、3 i和3 j对CDK 2/Cyclin A2具有特异性抑制活性，IC 50值分别为4.6、4.8和55μM。这三种化合物均能诱导人上皮癌细胞（HeLa）G1/S期阻滞，提示它们在体外可抑制CDK 2活性。此外，分子模拟研究，他们对接到细胞周期蛋白依赖性激酶2（CDK 2）的活性位点显示出较高的对接分数。这些数据表明，这三个化合物是研究细胞系统中激酶信号转导通路的良好的CDK 2抑制剂。
A series of purine nucleoside analogues bearing an aryl and hetaryl group in position 6 were prepared and their biological activities were assessed by in vitro CDK1/Cyclin B1 and CDK2/Cyclin A2 kinase assay. From the synthesized chemicals, three Xylocydine derivatives 3h, 3i, and 3j exhibited specific inhibitory activities on CDK2/Cyclin A2 with IC50values of 4.6, 4.8, and 55μM, respectively. Those three compounds all induced G1/S phase arrest in Human epithelial carcinoma cell line (HeLa), and the results suggested they may inhibit CDK2 activity in vitro. Furthermore, molecular modeling study, their docking into Cyclin Dependant Kinase 2 (CDK2) active site showed high docking scores. Taken together, these data suggest that, those three compounds are good inhibitors of CDK2 for studying this kinase signal transduction pathway in cell system.