Novel Transplatinum(II) Complexes with [N2O2] Donor Sets. Cellular Pharmacology and Apoptosis Induction in Pam 212-ras Cells

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.