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

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1和2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（I）=3．23×10^4L·mol^-1和Kb（2）=2．40×10^4L·mol^-1。配合物与BSA相互作用的研究表明，1和2均能与BSA发生较强的相互作用，结合常数均处在10^4-10^5L·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1和2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1和2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。

Interactions of benzimidazole derived mononuclear complexes, [M（EDTB）]2＋（M=Co^2＋ （1） and Ni^2＋ （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 3.23×10^4 L·mol^-1 and 2.40× 10^4 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 10^4-10^5 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^-4 mol· L^-1）.