title: Novel transplatinum(II) complexes with [N2O2] donor sets. Cellular pharmacology and apoptosis induction in Pam 212-ras cells.
abstract: 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.
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid, Spain.
authors.forename: Adoración G
authors.initials: AG
authors.lastname: Quiroga
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pérez
authors.forename: Carlos
authors.initials: C
authors.lastname: Alonso
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro-Ranninger
authors.forename: Nicholas
authors.initials: N
authors.lastname: Farrell
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000187:drug effects / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D008024:Ligands; D051379:Mice; D017672:Nitrogen Compounds / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D017672:Nitrogen Compounds; D009944:Organoplatinum Compounds; D004247:DNA