Quiroga Adoración G, Pérez Jose M, Alonso Carlos, Navarro-Ranninger Carmen, Farrell Nicholas
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain.
J Med Chem. 2006 Jan 12;49(1):224-31. doi: 10.1021/jm050804v.
Cellular pharmacological properties of eight trans-picoline platinum(II) complexes of formula trans-[PtX(2)(L)(L')], where X = Cl or CH(3)COO (OAc) and L = L' = 3-picoline (3-pic), 4-picoline (4-pic) or L = NH(3) and L' = 3-pic or 4-pic, were investigated in murine keratinocyte Pam 212 cells and Pam 212-ras cells, murine tumor keratinocytes derived from transformation with a viral vector containing the H-ras oncogene. The derivatives trans-[Pt(OAc)(2)(L)(L')] (L = L' = 3-pic, 9, and L = L' = 4-pic, 10) were able to circumvent resistance in Pam 212-ras cells. Although all the trans-picoline platinum(II) acetate derivatives showed a similar level of DNA binding, there were remarkable differences in cellular accumulation: the complexes having two picoline ligands (9, 10) had a much higher intracellular accumulation than those having mixed picoline and ammine ligands (11, 12). No significant differences in cellular pharmacological properties have been observed between isomers having 3- or 4-picoline.
研究了通式为反式-[PtX₂(L)(L')]的8种反式吡啶铂(II)配合物的细胞药理特性，其中X = Cl或CH₃COO（OAc），L = L' = 3-吡啶（3-pic）、4-吡啶（4-pic），或者L = NH₃且L' = 3-pic或4-pic。研究对象为小鼠角质形成细胞Pam 212细胞和Pam 212-ras细胞，后者是用含有H-ras癌基因的病毒载体转化得到的小鼠肿瘤角质形成细胞。反式-[Pt(OAc)₂(L)(L')]衍生物（L = L' = 3-pic，即9；L = L' = 4-pic，即10）能够克服Pam 212-ras细胞的耐药性。虽然所有反式吡啶铂(II)乙酸酯衍生物显示出相似水平的DNA结合，但细胞摄取存在显著差异：具有两个吡啶配体的配合物（9、10）比具有混合吡啶和氨配体的配合物（11、12）具有更高的细胞内摄取。在具有3-或4-吡啶的异构体之间未观察到细胞药理特性的显著差异。
