多吡啶类双核镍配合物的合成、晶体结构及抗癌活性

Synthesis,Structure and Anticancer Activity of Binuclear Polypyridine Nickel Complexes

合成了2个相似的多吡啶类双核镍配合物[Ni_(2)(L)2Cl_(2)](ClO_(4))2·3H_(2)O (1)和[Ni_(2)(L)2Cl_(2)](PF6)2 (2)(L=N,N-bis(pyridin-2-ylmethyl)-4-(4-((pyridin-2-ylmethyl)amino)benzyl)aniline),通过X射线单晶衍射对其结构进行测定并解析,并利用元素分析、红外光谱对其进行表征。另外,通过噻唑蓝(MTT)比色法检验了 2个配合物对HeLa细胞、BGC-823细胞、NCI-H_(4)60细胞以及HepG-2细胞的体外毒性作用,结果表明2个配合物均对NCI-H_(4)60细胞表现出良好的毒性作用,IC_(5)0值分别为(26.0±2.2)μmol·L^(-1)(1)和(31.3±2.7) μmol·L^(-1) (2)。进一步通过Hoechst 33342染色、活性氧水平检测、线粒体膜电位的测定和分析探究了配合物1的抗肿瘤作用机制,结果表明,该配合物可能通过线粒体途径来诱导细胞凋亡从而对癌细胞产生致死作用。

Two new polypyridine dinuclear nickel(Ⅱ) complexes [Ni_(2)(L)2 Cl_(2)](ClO_(4))2·3 H_(2) O(1) and [Ni_(2)(L)2 Cl_(2)](PF6)2(2)(L=N,N-bis(pyridin-2-ylmethyl)-4-(4-((pyridin-2-ylmethyl)amino)benzyl)aniline) were synthesized,and their structures were determined by X-ray single crystal diffraction,elemental analysis and infrared spectroscopy.Moreover,the in vitro toxic effects of the two complexes on cancer cells(HeLa,BGC-823,NCI-H_(4)60,HepG-2) were tested by thiazole blue(MTT) method,and the results indicate that the two complexes showed good toxicity on NCIH_(4)60 cells.IC_(5)0=(26.0±2.2) μmol·L^(-1)(1),(31.3±2.7)μmol·L^(-1)(2).The cytotoxic mechanism of complex 1 towards NCI-H_(4)60 cells was further explored by Hoechst 33342 staining,detection of intracellular reactive oxygen species levels and measurement of mitochondrial membrane potential change.The results demonstrate that complex 1 is likely to induce cell apoptosis through the mitochondrial pathway,thereby causing lethal effects on cancer cells.CCDC:2058250,1;2058251,2.