Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents
Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents
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新型合成吖啶衍生物作为有效的 DNA 结合和细胞凋亡诱导抗肿瘤剂
DOI：
10.1016/j.bmc.2013.05.008
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发表时间：
2013-07-15
影响因子：
3.5
通讯作者：
Jiang, Yuyang
中科院分区：
文献类型：
--
作者：
Lang, Xuliang;Li, Lulu;Jiang, Yuyang
吖啶衍生物已被探索作为DNA结合抗癌剂。一些衍生物显示出不期望的药代动力学性质，需要探索新的衍生物。在这项工作中，一系列新的吖啶类似物的合成，通过修改以前未开发的吖啶和苯之间的连接基团和它们的抗增殖活性和DNA结合能力进行了评价。在这些衍生物中，化合物5c表现出DNA结合能力和拓扑异构酶I抑制活性。在K562细胞系中，5c通过依赖于细胞因子的内在途径诱导细胞凋亡。这些数据表明，化合物5c和其他吖啶衍生物与吖啶和苯基团之间的修改连接可能是有效的DNA结合剂。(C)2013爱思唯尔有限公司保留所有权利。
Acridine derivatives have been explored as DNA-binding anticancer agents. Some derivatives show undesired pharmacokinetic properties and new derivatives need to be explored. In this work, a series of novel acridine analogues were synthesized by modifying previously unexplored linkers between the acridine and benzene groups and their antiproliferative activity and the DNA-binding ability were evaluated. Among these derivatives, compound 5c demonstrated DNA-binding capability and topoisomerase I inhibitory activity. In K562 cell lines, 5c induced apoptosis through mitochondria-dependent intrinsic pathways. These data suggested that compound 5c and other acridine derivatives with modified linkers between the acridine and benzene groups might be potent DNA-binding agents. (C) 2013 Elsevier Ltd. All rights reserved.