氨·二甲胺·羧酸根合铂(Ⅱ)类配合物的合成、抗肿瘤活性和与DNA的键合水平

本工作设计合成了6种新型混胺羧酸根合铂(Ⅱ)类配合物Pt((?)NH)(NH₃)X₂](a～f){其中，X=CH₃COO^-(乙酸根)，CH₃Cl COO^-(氯乙酸根)，CHCl₂COO^-(二氯乙酸根)，C₆H₅-COO^-(苯甲酸根)，p-CH₃-C₆H₄-COO^-(对甲基苯甲酸根)，p-CH₃O-C₆H₄-COO^-(对甲氧基苯甲酸根)}。通过元素分析、摩尔电导、差热分析、红外光谱、紫外光谱和 ¹H核磁共振谱对配合物进行了表征。通过MTT法研究了配合物的体外抗肿瘤活性，通过等离子体质谱研究了配合物与细胞DNA的键合量；体外抗肿瘤活性测试表明，配合物(a～f)对所测试的肿瘤细胞MCF-7、HCT-8和BGC-823没有表现出活性，但对EJ和HL-60两种肿瘤细胞表现出好的活性，而且配合物(d～f)对HL-60细胞的活性与顺铂相当。配合物(a～f)与HL-60细胞的DNA键合量与其作用浓度表现出一定的依赖性，从小到大的顺序为：cisplatin < c < b < a < f < e < d。

Synthesis,Cytotoxicity and DNA-binding Levels of Ammine/Dimethylamine Platinum(Ⅱ) Complexes with Carboxylates

Six new ammine/dimethylamine platinum(Ⅱ)complexes with earboxylates(a～f)have been synthesized and characterized by elemental analysis,conductivity,thermal analysis,IR,UV,and1 H NMR techniques.The cytotoxicity of the complexes was tested by MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)assay.The levels of total platinum bound to DNA were measured by ICP-MS.The results show that the complexes(a～f)have selectivity against tested carcinomas,have no cytotoxicity against HCT-8,BGC-823 and MCF7,but have better cytotoxicity against EJ and HL-60,moreover,cytotoxicity of complexes(d～f)against HL-60 is similar to that of cisplatin.The levels of total platinum bound to DNA in HL-60 are increased with increasing concentrations,and the levels of total platinum bound to DNA increase in the following sequence:cisplatin＜C＜b＜a＜f＜e＜d.