以DNA为靶点的钌(Ⅱ)配合物的合成、晶体结构和抗肿瘤活性

Synthesis,Crystal Structure and Cytotoxicity of Ru(Ⅱ) Complex Targeting DNA

为开发新型钌(Ru)抗肿瘤药物,以3-甲基-2-噻吩甲醛-4-羟基苯甲酰肼席夫碱配体(L)合成了[Ru(L)(DMSO)2Cl2](1)(DMSO=二甲基亚砜)。用X射线单晶衍射法测定了1的晶体结构。配合物1的结构由1个Ru(Ⅱ)中心离子与2个DMSO分子、2个氯离子、1个L配位而成。通过MTT实验分析,1对T24细胞表现出良好的抗肿瘤活性。同时,通过彗星实验、蛋白质印迹实验和DNA琼脂糖凝胶电泳实验结果证明1可以有效结合DNA,诱导DNA损伤,最终杀死肿瘤细胞。导致DNA损伤的原因很可能是由于细胞与1孵育后细胞内可以产生大量的活性氧。

To develop a novel antitumor Ru agent,[Ru(L)(DMSO)2 Cl2](1)(DMSO=dimethyl sulfoxide) was synthesized by employing a Schiff base ligand 3-methyl-2-thiophenecarboxaldehyde-4-hydroxybenzhydrazide(L).The single crystal X-ray crystallographic study was carried out to determine the crystallographic structure of 1.The structure of complex 1 is composed of a central Ru(Ⅱ) ion,two DMSO molecules,two chloride ions,and a ligand L.In addition,1 possessed strong antitumor activity against T24 cells by MTT analysis.Furthermore,the potential antitumor mechanism of 1 was investigated by comet assays,western-blotting assays,and DNA agarose gel electrophoresis.These results indicate that 1 can effectively bind to DNA and induce DNA damage,and eventually kill the tumor cells.DNA damage may be caused by the production of reactive oxygen species.CCDC:2080249.