摘要
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 synthesize novel platinum（II） complexes by the choices of the chiral centers in carrier groups and leaving groups,so as to improve the water solubility,and to find out the new platinum（II） complexes with good activities.Methods：（1R,2R）-N1-（pyridine-2-ylmethyl） cyclohexane-1,2-diamine（LR） and（1S,2S）-N1-（pyridine-2-ylmethyl） cyclohexane-1,2-diamine（LS） were designed and synthesized.The platinum（II） complexes were synthesized by using LR and LS as carrier ligands,and using chloride,sulfate,oxalate,malonate,1,4-butyldicarboxylate and 1,1-cyclobutyldicarboxylate anions as leaving groups.The in vitro cytotoxicity of the target compounds on human lung cancer A549,human colon cancer cell line HCT-116,human hepatoma cell line HepG2 and human breast cancer cell line MCF-7 were tested by MTT method.Results：Twelve platinum（II） complexes were synthesized and their structures were determined by elemental analysis,IR,1H-NMR and ESI-MS spectra.These platinum（II） complexes overcame the problem of poor water-solubility,and exhibited general activity to MCF-7 cell line.Conclusion：The target compounds are synthesized successfully by the choices of leaving groups and chiral centers in carrier ligands on the basis of structure of oxaliplatin.It can provide a guidance for the design of more reasonable oxaliplatin analogues containing chiral centers.
出处
《药学进展》
CAS
2011年第12期560-565,共6页
Progress in Pharmaceutical Sciences
