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目的:选择合适的载体基团手性中心及离去基团,合成新型铂(Ⅱ)配合物,改善水溶性,寻找抗肿瘤活性好的铂(Ⅱ)配合物。方法:合成(1R,2R)-N1-(2-亚甲基吡啶)-1,2-环己二胺和(1S,2S)-N1-(2-亚甲基吡啶)-1,2-环己二胺,并以这两个化合物为载体基团配体,选用氯离子、硫酸根、草酸根、丙二酸根、1,4-丁二酸根、1,1-环丁二羧酸根为离去基团,合成新型铂(Ⅱ)配合物。采用MTT法测定配合物对人肺癌细胞A549、人结肠癌细胞HCT-116、人肝癌细胞HepG2和人乳腺癌细胞MCF-7的体外抗肿瘤活性。结果:合成了12个目标化合物,其结构均经元素分析、红外光谱、核磁共振氢谱和电喷雾质谱等确证。所得铂(Ⅱ)配合物可很好地克服铂类抗肿瘤药物水溶性差的问题,其对不同肿瘤细胞显示出不同的抗肿瘤活性,其中对人乳腺癌细胞MCF-7作用较为明显。结论:在奥沙利铂结构的基础上,利用载体基团手性中心及离去基团的选择合成新型铂配合物,为设计更为合理的含手性中心的奥沙利铂类似物提供了指导。
OBJECTIVE: To select a suitable chiral center and leaving group for the carrier, to synthesize a novel platinum (Ⅱ) complex, to improve its water solubility and to find a platinum (Ⅱ) complex with good antitumor activity. Methods: The synthesis of (1R, 2R) -N1- (2-methylenepyridine) -1,2-cyclohexanediamine and (1S, 2S) -N1- (2-methylenepyridine) Cyclohexane diamine, and the two compounds as a carrier group ligands, the choice of chloride, sulfate, oxalate, malonate, 1,4-succinate, 1,1-cyclobutane dicarboxylate is Leaving groups, the synthesis of new platinum (Ⅱ) complexes. The antitumor activity of the complex in human lung cancer cell line A549, human colon cancer cell line HCT-116, human hepatoma cell line HepG2 and human breast cancer cell line MCF-7 was determined by MTT assay. Results: Twelve target compounds were synthesized and their structures were confirmed by elemental analysis, IR, 1HNMR and electrospray ionization mass spectrometry. The obtained platinum (Ⅱ) complex can well overcome the problem of poor water-solubility of platinum antitumor drugs, which shows different antitumor activity to different tumor cells, and the effect on the human breast cancer cell MCF-7 is obvious. Conclusion: Based on the structure of oxaliplatin, the novel platinum complexes were synthesized by the selection of chiral centers and leaving groups of carrier groups, which provided a more reasonable method to design oxaliplatin analogues containing chiral centers Guidance.