作为高效拓扑异构酶II抑制剂的苯并咪唑-罗丹宁缀合物的设计、合成及生物学评价
Design, synthesis and biological evaluation of benzimidazole-rhodanine conjugates as potent topoisomerase II inhibitors.
作者信息
Li Penghui, Zhang Wenjin, Jiang Hong, Li Yongliang, Dong Changzhi, Chen Huixiong, Zhang Kun, Du Zhiyun
机构信息
Institute of Natural Medicine & Green Chemistry , School of Chemical Engineering and Light Industry , Guandong University of Technology , Guangzhou 510006 , China . Email:
Universite Paris Diderot , Sorbonne Paris Cite , ITODYS , UMR 7086 CNRS , 15 rue J-A de Baif , 75270 Cedex 13 Paris , France.
出版信息
Medchemcomm. 2018 Jun 2;9(7):1194-1205. doi: 10.1039/c8md00278a. eCollection 2018 Jul 1.
In this study, a series of benzimidazole-rhodanine conjugates were designed, synthesized and investigated for their topoisomerase II (Topo II) inhibitory and cytotoxic activities. The results from Topo II-mediated pBR322 DNA relaxation and cleavage assays showed that the synthesized compounds might act as Topo II catalytic inhibitors. Certain compounds displayed potent Topo II inhibition at 10 μM. The cytotoxic activities of these compounds against HeLa, A549, Raji, PC-3, MDA-MB-201, and HL-60 cancer cell lines were evaluated. The results indicated that these compounds exhibited strong antiproliferative activity. A good relationship was observed between the Topo II inhibitory potency and the cytotoxicity of these compounds. The structure-activity relationship revealed that the electronic effects, the phenyl group, and the rhodanine moiety were particularly important for the Topo II inhibitory potency and cytotoxicity.
在本研究中，设计、合成了一系列苯并咪唑-若丹宁共轭物，并对其拓扑异构酶II（Topo II）抑制活性和细胞毒性进行了研究。Topo II介导的pBR322 DNA松弛和切割试验结果表明，合成的化合物可能作为Topo II催化抑制剂。某些化合物在10 μM时表现出强效的Topo II抑制作用。评估了这些化合物对HeLa、A549、Raji、PC-3、MDA-MB-201和HL-60癌细胞系的细胞毒性。结果表明，这些化合物表现出较强的抗增殖活性。观察到这些化合物的Topo II抑制效力与细胞毒性之间存在良好的关系。构效关系表明，电子效应、苯基和若丹宁部分对Topo II抑制效力和细胞毒性尤为重要。
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