5-甲基-2-(2'-吡啶基)苯并咪唑及甘氨酸根铜(Ⅱ)配合物的合成、DNA结合及抗癌活性
Synthesis, DNA Interaction and Anticancer Activity of Mixed-Ligand Copper(Ⅱ) Complex of 5-Methyl-2-(2'-pyridyl)benzimidazole and Glycinate
作者单位E-mail
莫慧雯 华南农业大学材料与能源学院应用化学系, 广州 510642  
刘雅娴 华南农业大学材料与能源学院应用化学系, 广州 510642  
蔡戴宏 华南农业大学材料与能源学院应用化学系, 广州 510642  
沈芳 华南农业大学材料与能源学院应用化学系, 广州 510642  
乐学义 华南农业大学材料与能源学院应用化学系, 广州 510642 lexyfu@163.com 
摘要: 利用溶剂缓慢挥发法合成了以5-甲基-2-(2'-吡啶基)苯并咪唑为主配体的铜(Ⅱ)混配配合物[Cu(HPBM)(Gly)(H2O)]ClO4·0.5H2O(HPBM=5-甲基-2-(2'-吡啶基)苯并咪唑,Gly=甘氨酸根)。采用元素分析、红外光谱、紫外可见光谱、摩尔电导率测定和ESI-MS等手段对配合物进行了表征。应用电子吸收光谱、荧光光谱、粘度测定及分子对接等方法揭示了配合物主要以沟槽结合的方式与DNA作用。应用MTT法测定了配合物对Eca-109、HeLa和A549细胞株的体外细胞毒活性,其IC50值范围为6.4~8.5 μmol·L-1。尤为重要的是,通过AO/EB双染法、单细胞凝胶电泳、线粒体膜电位及细胞周期测定分析等揭示了配合物通过DNA结合及线粒体功能失调途径诱导Eca-109细胞凋亡。
关键词: 铜(Ⅱ)配合物  5-甲基-2-(2'-吡啶基)苯并咪唑  甘氨酸  DNA结合  抗癌作用
基金项目: 广东省自然科学基金(No.2015A030313423)和广东省大学生创新训练项目(No.201710564307)资助
Abstract: A new copper(Ⅱ) complex[Cu(HPBM)(Gly)(H2O)]ClO4·0.5H2O (HPBM=5-methyl-2-(2'-pyridyl)benzi-midazole, Gly=Glycinate), was prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, molar conductivity and ESI-MS spectroscopy. Electronic absorption spectroscopy, EB-DNA fluorescence quenching spectroscopy, viscosity measurement and molecular docking revealed that the complex could interact with CT-DNA through a minor groove binding mode. The cytotoxic activity in vitro of the complex against Eca-109, HeLa and A549 cell lines was evaluated by MTT method. The IC50 values ranged from 6.4 to 8.5 μmol·L-1. AO/EB double staining analysis indicated that the complex could induce apoptosis in Eca-109 cells. The comet assays demonstrated that the complex could damage DNA in Eca-109 cells, which further revealed that the complex could cause apoptosis in the cells. The mitochondrial membrane potential studies showed that the complex could induce decrease in the intracellular mitochondrial membrane potential. Moreover, the cell cycle arrest of Eca-109 cell lines was investigated by flow cytometry. The results demonstrated that the complex can induce apoptosis in Eca-109 cell through DNA interaction and mitochondria dysfunctional pathways.
Keywords: copper(Ⅱ) complex  5-methyl-2-(2'-pyridyl)benzimidazole  glycine  DNA interaction  anticancer activity
投稿时间:2018-10-21 修订日期:2018-12-16
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莫慧雯,刘雅娴,蔡戴宏,沈芳,乐学义.5-甲基-2-(2'-吡啶基)苯并咪唑及甘氨酸根铜(Ⅱ)配合物的合成、DNA结合及抗癌活性[J].无机化学学报,2019,35(3):477-484.
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