Zhang Jinchao, Zhao Xuejun
Department of Chemistry, College of Chemistry & Environmental Science, Hebei University, Baoding 071002, PR China.
Eur J Med Chem. 2007 Feb;42(2):286-91. doi: 10.1016/j.ejmech.2006.09.013. Epub 2006 Nov 3.
Seven new mixed ammine/propylamine platinum(II) complexes with carboxylates (a-g) have been synthesized and characterized by elemental analysis, conductivity, IR, UV, and (1)H NMR spectra techniques. The cytotoxicity of these complexes was tested by MTT assay. The levels of total platinum bound to DNA were measured by ICP-MS. The results indicate that the complexes (a-g) have better cytotoxicity against EJ and HL-60 than other carcinoma cell lines. The cytotoxicity increases in the sequence: g<f<e<d<b<c<a against tested carcinoma cell lines. The cytotoxicity of complexes (a-c) is equal to that of cisplatin against HL-60. The cytotoxicity of complex a is also equal to that of cisplatin against EJ. However, the complexes (a-g) are significantly less potent than cisplatin against BGC-823, HCT-8 and MCF-7. The total DNA-platination levels increase in the sequence: cisplatin<g<e<f<d<b<c<a under the same experimental conditions. It suggests that there is no correlation between total DNA-platination levels in HL-60 cells and cytotoxicity of ammine/propylamine platinum complexes. When leaving groups are aromatic carboxylates, the complexes have better cytotoxicity, and moreover, the substituent in benzene ring also influences cytotoxicity.
合成了七种新的含羧酸盐的氨/丙胺合铂（II）混合配合物（a - g），并通过元素分析、电导率、红外光谱、紫外光谱和核磁共振氢谱技术对其进行了表征。通过MTT法检测了这些配合物的细胞毒性。用ICP - MS测定了与DNA结合的总铂含量。结果表明，配合物（a - g）对EJ和HL - 60的细胞毒性优于其他癌细胞系。对受试癌细胞系而言，细胞毒性按g < f < e < d < b < c < a的顺序增加。配合物（a - c）对HL - 60的细胞毒性与顺铂相当。配合物a对EJ的细胞毒性也与顺铂相当。然而，配合物（a - g）对BGC - 823、HCT - 8和MCF - 7的效力明显低于顺铂。在相同实验条件下与DNA结合的总铂含量按顺铂 < g < e < f < d < b < c < a的顺序增加。这表明HL - 60细胞中与DNA结合的总铂含量与氨/丙胺铂配合物的细胞毒性之间没有相关性。当离去基团为芳香羧酸盐时，配合物具有更好的细胞毒性，而且苯环上的取代基也会影响细胞毒性。
