苯并咪唑衍生的单核钴(Ⅱ)和单核镍(Ⅱ)配合物与DNA和蛋白质的结合反应性及细胞毒活性研究
Reactivities Towards DNA and Protein and Cytotoxic Activities of Benzimidazole Derived Mononuclear Cobalt(Ⅱ) and Nickel(Ⅱ) Complexes
作者单位E-mail
陈战芬 华中科技大学化学与化工学院, 武汉 430074
湖北师范学院化学与化工学院, 污染物分析与资源化技术湖北省重点实验室, 稀有金属化学湖北省协同创新中心, 黄石 435002 
chenzf1979@163.com 
马艺丹 湖北师范学院化学与化工学院, 污染物分析与资源化技术湖北省重点实验室, 稀有金属化学湖北省协同创新中心, 黄石 435002  
华罗光 湖北师范学院化学与化工学院, 污染物分析与资源化技术湖北省重点实验室, 稀有金属化学湖北省协同创新中心, 黄石 435002  
张健 湖北师范学院化学与化工学院, 污染物分析与资源化技术湖北省重点实验室, 稀有金属化学湖北省协同创新中心, 黄石 435002  
摘要: 利用紫外吸收光谱、荧光光谱、圆二色光谱(CD)等各种光谱手段对比地研究了由苯并咪唑衍生的单核钴配合物 [Co(EDTB)]2+1)和单核镍配合物 [Ni(EDTB)]2+2)(这里EDTB为N,N,N’,N’-四(2’-苯并咪唑甲基)-1,2-乙二胺)与小牛胸腺DNA(CT-DNA)和牛血清白蛋白(BSA)的相互作用。结果表明,在生理条件下,配合物12均能通过插入方式较强的与CT-DNA结合,诱导DNA构象的改变;且配合物1对DNA的结合能力略强于2,其结合常数分别为Kb(1)=3.23×104 L·mol-1Kb(2)=2.40×104 L· mol-1.配合物与BSA相互作用的研究表明,12均能与BSA发生较强的相互作用,结合常数均处在104~105 L·mol-1;该结合引起了BSA微环境和构象发生变化,且使BSA内源荧光被淬灭,淬灭机理为静态淬灭。利用MTT法研究了配合物12对小鼠白血病细胞株P388和人非小细胞肺癌细胞株A-549的体外细胞毒活性,实验结果表明,配合物12对P388不敏感,对A-549在高浓度(10-4~10-5 mol·L-1)下表现出与顺铂相当的细胞毒活性。
关键词: 单核钴配合物  单核镍配合物  DNA  BSA  结合反应性  细胞毒活性
基金项目: 国家自然科学基金青年(No.21301056);湖北省教育厅优秀中青年人才科研课题(No.Q20092201);中国博士后科学基金面上(No.2012M521419)资助项目。
Abstract: Interactions of benzimidazole derived mononuclear complexes, [M(EDTB)]2+(M=Co2+ (1) and Ni2+ (2), EDTB=N, N, N', N'-tetrakis(2'-benzimidazolyl methyl)-1,2-ethanediamine), with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) were been investigated by UV-Vis absorption, fluorescence and circular dichroism (CD). The experimental results suggested that under physiological conditions the two complexes could strongly bind to CT-DNA by the intercalation mode and induce remarkable conformational variations of DNA. And DNA binding ability of 1 is slightly higher than that of 2, whose binding constants (Kb) are 3.23×104 L·mol-1 and 2.40×104 L·mol-1, respectively. In view of the results of the reactivity towards BSA, complexes 1 and 2 could also strongly interact with BSA with binding constants of 104~105 L·mol-1 and induce micro environmental and conformational variation of BSA. The associations between the two complexes and BSA quench the intrinsic fluorescence of BSA through a static quenching mechanism. In vitro cytotoxic activities of complexes 1 and 2 against the murine leukemia cell line P388 and the human non-small-cell lung cancer cell line A-549 were studied by MTT assay method. The results indicated that complexes 1 and 2 were not sensitive to the P388 tumor cell line and showed comparable cytotoxicity to cisplatin against the A-549 cell line at high concentrations (10-4~10-5 mol·L-1).
Keywords: mononuclear cobalt(Ⅱ) complex  mononuclear nickel(Ⅱ) complex  DNA  BSA  reactivities  cytotoxic activities
投稿时间:2013-11-09 修订日期:2014-03-31
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陈战芬,马艺丹,华罗光,张健.苯并咪唑衍生的单核钴(Ⅱ)和单核镍(Ⅱ)配合物与DNA和蛋白质的结合反应性及细胞毒活性研究[J].无机化学学报,2014,30(7):1525-1534.
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