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: Adoración G Quiroga, Jose M Pérez, Carlos Alonso, Carmen Navarro-Ranninger, Nicholas Farrell
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 49 Issue 1 Pg. 224-31 (Jan 12 2006) ISSN: 0022-2623 [Print] United States
• PMID: 16392807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Ligands
• Nitrogen Compounds
• Organoplatinum Compounds
• DNA

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line
• DNA (drug effects, genetics)
• Drug Screening Assays, Antitumor
• Ligands
• Mice
• Nitrogen Compounds (chemistry)
• Organoplatinum Compounds (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism