State Key Laboratory for Platinum Group Metals, Kunming Institute of Precious Metals, 650106 Yunnan, China.
Sci Rep. 2013;3:2464. doi: 10.1038/srep02464.
Two mixed-NH3/amine platinum (II) complexes of 3-dichoroacetoxylcyclobutane-1, 1-dicarboxylate have been prepared in the present study and characterized by elemental analysis and IR, HPLC-MS and (1)H, (13)C-NMR. The complexes exist in equilibrium between two position isomeric forms and undergo hydrolysis reaction in aqueous solution, releasing the platinum pharmacophores and dichloroacetate which is a small-molecular cell apoptosis inducer. Both complexes were evaluated for in vitro cytotoxic profile in A549, SGC-7901 and SK-OV-3 cancer cells as well as in BEAS-2B normal cells. They exhibit markedly cytotoxicity toward cancer cells by selectively inducing the apoptosis of cancer cells, whereas leaving normal cells less affected. They have also the ability to overcome the resistance of SK-OV-3 cancer cells to cisplatin. Our findings offer an alternative novel way to develop platinum drugs which can both overcome the drug resistance and selectively target tumor cells.
本研究制备了两种混合 NH3/胺铂（II）配合物的 3-二氯乙酰氧基环丁烷-1,1-二羧酸酯，并通过元素分析、IR、HPLC-MS 和（1）H、（13）C-NMR 进行了表征。这些配合物在两种位置异构形式之间存在平衡，并在水溶液中发生水解反应，释放出铂药效团和二氯乙酸，后者是一种小分子细胞凋亡诱导剂。两种配合物均在 A549、SGC-7901 和 SK-OV-3 癌细胞以及 BEAS-2B 正常细胞中进行了体外细胞毒性评价。它们通过选择性诱导癌细胞凋亡对癌细胞表现出明显的细胞毒性，而对正常细胞的影响较小。它们还具有克服 SK-OV-3 癌细胞对顺铂耐药性的能力。我们的研究结果为开发既能克服耐药性又能选择性靶向肿瘤细胞的铂类药物提供了一种新的替代方法。
