Pharmaceutical Research Center, School of Chemistry & Chemical Engineering, Southeast University, Nanjing 211189, China.
Eur J Med Chem. 2011 Oct;46(10):5146-53. doi: 10.1016/j.ejmech.2011.08.029. Epub 2011 Aug 26.
A novel series of ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been synthesized and characterized. All complexes were characterized by elemental analysis, IR, (1)H NMR, and ESI-MS spectra. The in vitro antiproliferative activities of the platinum-based compounds have been investigated against several human cancer cell lines, indicating that complexes 1 and 11 showed comparable cytotoxicity to those of cisplatin and oxaliplatin against four cell lines, superior to that of carboplatin. The results of drug safety evaluation (acute toxicity study) showed that complex 11 was much less toxic than cisplatin and oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the binding affinity of complexes with pET22b plasmid DNA.
已合成并表征了一系列新型的氨/环己胺铂（II）配合物，其离去基团为 1-（取代苄基）氮杂环丁烷-3,3-二羧酸酯。所有配合物均通过元素分析、IR、（1）H NMR 和 ESI-MS 光谱进行了表征。铂类化合物对几种人癌细胞系的体外增殖活性进行了研究，结果表明配合物 1 和 11 对四种细胞系的细胞毒性与顺铂和奥沙利铂相当，优于卡铂。药物安全性评价（急性毒性研究）的结果表明，配合物 11 的毒性明显低于顺铂和奥沙利铂。流式细胞术和琼脂糖凝胶电泳研究表明，两种配合物 1 和 11 均诱导肿瘤细胞凋亡，并证明了配合物与 pET22b 质粒 DNA 的结合亲和力。
