Liu Xia, Shen Hong, Zhu Haibin, Cui Kai, Gou Shaohua
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China.
Bioorg Med Chem Lett. 2007 Jul 15;17(14):3831-4. doi: 10.1016/j.bmcl.2007.05.014. Epub 2007 May 13.
A series of novel cisplatin-type platinum complexes were designed, characteristic of epoxysuccinates as leaving groups. The pertinent compounds were prepared and characterized by IR, (1)H NMR, and ESI-MS spectra with elementary analyses. The in vitro cytotoxic activities of compounds toward SPC-A1 human lung adenocarcinoma cell line and BGC823 human stomach adenocarcinoma cell line were determined. Biological tests have confirmed that complexes containing 4R,5R-DMID [abbreviation of (4R,5R)-4,5-bis (aminomethyl)-2-isopropyl-1,3-dioxolane] as carrier ligands have greater cytotoxicity toward tumor cells than the corresponding compounds with other carrier ligands. Most platinum complexes with trans-epoxysuccinates usually have higher cytotoxicity than those with cis-epoxysuccinates. Complex 4a shows the most effective among those tested platinum complexes in both cell lines, and its cytotoxicity approached that of cisplatin.
设计了一系列新型顺铂类铂配合物，其特征是环氧琥珀酸酯作为离去基团。制备了相关化合物，并通过红外光谱、¹H核磁共振谱和电喷雾电离质谱以及元素分析对其进行了表征。测定了这些化合物对SPC - A1人肺腺癌细胞系和BGC823人胃腺癌细胞系的体外细胞毒性活性。生物学测试证实，含有4R,5R - DMID [（4R,5R）- 4,5 - 双（氨甲基）- 2 - 异丙基 - 1,3 - 二氧戊环的缩写]作为载体配体的配合物对肿瘤细胞的细胞毒性比具有其他载体配体的相应化合物更大。大多数含有反式环氧琥珀酸酯的铂配合物通常比含有顺式环氧琥珀酸酯的铂配合物具有更高的细胞毒性。配合物4a在两种细胞系中测试的铂配合物中显示出最有效的效果，其细胞毒性接近顺铂。
