钌多吡啶配合物与DNA作用及抗肿瘤活性(英文)

DNA Interaction and Antitumor Activities of Ruthenium(Ⅱ) Polypyridyl Complex

应用电子吸收光谱、荧光光谱和粘度测定等方法研究钌多吡啶配合物[Ru(phen)2(Hecip)]2(phen=1,10-邻菲啰啉,Hecip=2(9-乙基-9H-咔唑-3-基)-1H-咪唑并[4,5-f][1,10]菲啰啉)与DNA相互作用。结果表明配合物与DNA键合计量比为2∶1,键合常数超过105mol-1.L,配合物以插入方式与DNA结合。运用琼脂糖凝胶电泳实验研究配合物诱导pBR322DNA断裂及断裂机理。体外抗肿瘤活性结果表明配合物能有效抑制肿瘤细胞增殖,进一步研究表明配合物可以将细胞周期阻滞在S期。

The interactions of the Ru（Ⅱ） complex, [Ru（phen）2（Hecip）]2＋ （phen=1,10-phenanthroline, Hecip=N-ethyl-4-（[1,10]-phenanthroline[5,6-f]imidazol-2-yl）carbazole）, with calf thymus DNA （CT DNA） were studied by using absorption spectroscopy, binding stoichiometry, viscosity measurement and photoactivated cleavage. A tight 2：1 complex is formed by the Ru（Ⅱ） polypyridyl complex and CT DNA with a binding constant exceeding 105 mol-1·L and with a binding mode of intercalation. Furthermore, the complex exhibits efficient DNA cleavage activity on UV （365 nm） irradiation via a mechanistic pathway involving formation of singlet oxygen as the reactive species. On the other hand, the cytotoxic activity of the complex was tested by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide （MTT） method. The complex shows prominent anticancer activity against selected tumor cell lines with IC50 values lower than those of cisplatin. Further flow cytometry experiments show that the cytotoxic Ru（Ⅱ） complex can cause cell cycle arrest in the S phase.