邻香草醛缩胡椒乙胺席夫碱锌(Ⅱ)配合物的研究

Crystal Structure and Antitumor Activity of Zinc (Ⅱ) Complex with Schiff Bases Derived from 2-Hydroxy-3-methoxybenzaldehyde and 2-(3,4-Methylenedioxyphenyl)ethylamine

本文以邻香草醛缩胡椒乙胺席夫碱(L)为配体,合成一种新的席夫碱-锌(Ⅱ)双核配合物[Zn2(L)2Cl2](1),并通过谱学分析及X射线单晶衍射分析对配合物1进行结构表征,通过MTT法测试配合物1及L对6种人肿瘤细胞株和人正常肝细胞株HL-7702的体外增殖抑制活性。结果显示,配合物1对所有肿瘤株的增殖抑制率均高于配体,但低于顺铂;对HL-7702,其细胞毒性也远低于顺铂,且略低于配体,表现出一定的细胞毒性选择性。在分子水平上,通过荧光光谱法和凝胶电泳实验研究配合物1及L与DNA的作用机制。结果显示,配合物1以经典插入方式与DNA结合,而L对DNA的插入作用弱,表明柔性配体L与锌(Ⅱ)配位后,芳香平面结构刚性增强,使配合物1对DNA插入作用增强,从而能够通过阻碍肿瘤细胞DNA复制而表现显著高于L的抗肿瘤活性。

2-（3,4-Methylenedioxyphenyl）ethylamine and 2-hydroxy-3-methoxybenzaldehyde were selected to synthesize a new Schiff base（L）as bioactive ligand.The reaction of L with ZnCl2·2H2O afforded the binuclear zinc（Ⅱ）complex（1）,which was structurally characterized by IR,elemental analysis,ESI-MS,and single crystal X-ray diffraction analysis.The in vitro cytotoxicity of 1 against six human tumor cell lines（A549,MDA-MB-231,HeLa229,MGC80-3,A375,BEL-7404）and HL-7702 normal liver cell line was screened by MTT assay.The growth inhibition ratios of 1 were found to be higher than those of L against all the tumor cell lines,but lower than those of cisplatin.However,the cytotoxicity of 1 against HL-7702 was much lower than those of cisplatin,suggesting the cytotoxic selectivity of1.On the molecular level,the DNA binding property of 1 as well as L was studied by fluorescence spectroscopy and gel electrophoresis assay.The results indicated that complex 1 intercalatively bound with DNA,while the intercalative binding ability of L was very weak.It may be ascribed to the much more rigid aromatic planar structure of 1than L,which will facilitate the intercalative binding of 1 with DNA to effectively block the DNA replications in tumor cells,and higher antitumor activity of 1 can be obtained than L.