Synthesis and cytotoxicity of diam(m)ineplatinum(II) complexes with 2,2-bis(hydroxymethyl)malonate as the leaving group

Bioorg Med Chem Lett. 2012 Mar 15;22(6):2239-41. doi: 10.1016/j.bmcl.2012.01.091. Epub 2012 Feb 2.

Abstract

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / pharmacology
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Inhibitory Concentration 50
  • Lethal Dose 50
  • Magnetic Resonance Spectroscopy
  • Malonates / chemical synthesis*
  • Malonates / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Malonates
  • Organoplatinum Compounds
  • Oxaliplatin