氨·环己胺·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种新型氨·环己胺·羧酸根合铂!类配合物[Pt(NH3)(NH2)X2](a￣f)｛其中,X=CH3COO-(乙酸根),CH2ClCOO-(氯乙酸根),C6H5-COO-(苯甲酸根),p-CH3O-C6H4-COO-(对甲氧基苯甲酸根),p-CH3-C6H4-COO-(对甲基苯甲酸根),p-NO2-C6H4-COO-(对硝基苯甲酸根)｝。通过元素分析、摩尔电导、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,通过流式细胞仪以及等离子体质谱研究了配合物对细胞周期的影响以及与细胞DNA的键合量;体外抗肿瘤活性测试表明,配合物(c￣f)对EJ和HL-602种肿瘤细胞表现出好的活性,而且配合物(c),(d)和(e)对EJ和HL-602种肿瘤细胞的活性高于临床用药顺铂;配合物(a￣f)对MCF-7、HCT-8和BGC-8233种肿瘤细胞的活性低于顺铂;它们能阻止HL-60和EJ细胞G2 M→G1期的进行;配合物(a￣f)与HL-60和EJ细胞的DNA键合量从大到小的顺序为:c>d>e>cisplatin>f>a>b。

Synthesis, Cytotoxicity and DNA-Binding Levels of Amminecyclohexy/Aminecarboxy/Platinum(Ⅱ) Complexes

Six new amminecyclohexy/aminecarboxy/platinum(Ⅱ) complexes with carboxylates (a～f) have been synthesized and characterized by elemental analysis, conductivity, IR, UV, and 1H NMR spectra techniques. The cytotoxicity of the complexes was tested by MTT assay. The cell cycle analysis and the levels of total platinum bound to DNA were measured by flow cytometry and ICP-MS. The results show that complexes (c), (d), (e) and (f) have excellent cytotoxicity against EJ and HL-60 and complexes (c), (d) and (e) demonstrate cytotoxicity superiorto that of the clinically established cisplatin. Complexes (a～f) have poor cytotoxicity against HCT-8, MCF-7 and BGC-823 than that of cisplatin. The complexes (a～f) induce a concentration-dependent accumulation of HL-60 and EJ cells in the G2/M phase of the cell cycle as cisplatin. The levels of total platinum bound to DNA in HL-60 and EJ cells decrease in the sequence: c ＞ d ＞ e ＞ cisplatin ＞ f ＞ a ＞ b under the same experimental conditions.