State Key Laboratory of Advanced Technologies for Platinum Metals, Kunming Institute of Precious Metals, Yunnan, China.
Bioorg Med Chem Lett. 2012 Mar 15;22(6):2239-41. doi: 10.1016/j.bmcl.2012.01.091. Epub 2012 Feb 2.
Six diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group were synthesized and characterized by elemental analysis, FAB-MS, FT-IR, (1)H and (13)C NMR along with a single crystal X-ray diffraction for a representative compound. All the complexes were evaluated for the cytotoxicity against human cancer cell lines A549/ATCC, HT-29, SGC-7901. The activity is related to the nature of the am(m)ine ligand. cis-[Pt(II)(1R,2R-Diaminocyclohexane)·2,2-bis(hydroxymethyl)malonate] (complex 5) exhibits the greatest activity among those six complexes, and is even more active than its parent compound oxaliplatin. LD(50) was found to be 115 mg/kg by iv administration to ICR mice, much larger than that of oxaliplatin (LD(50)=19 mg/kg).
合成了 6 种以 2,2-双(羟甲基)丙二酸为离去基团的二(乙二胺)合铂(II)配合物，并通过元素分析、FAB-MS、FT-IR、(1)H 和(13)C NMR 以及代表化合物的单晶 X 射线衍射对其进行了表征。所有配合物均对人癌细胞系 A549/ATCC、HT-29、SGC-7901 的细胞毒性进行了评价。活性与胺配体的性质有关。顺-[Pt(II)(1R,2R-二氨基环己烷)·2,2-双(羟甲基)丙二酸](配合物 5)在这 6 种配合物中表现出最大的活性，甚至比其母体化合物奥沙利铂更具活性。通过静脉注射给药至 ICR 小鼠，发现 LD(50)为 115mg/kg，远大于奥沙利铂(LD(50)=19mg/kg)。
