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New trans dichloro (triphenylphosphine)platinum(II) complexes containing N-(butyl),N-(arylmethyl)amino ligands: Synthesis, cytotoxicity and mechanism of action

Bioorg Med Chem. 2016 Jul 1;24(13):2929-2937. doi: 10.1016/j.bmc.2016.04.067. Epub 2016 May 2.

Abstract

Some new platinum(II) complexes have been prepared, of general formula trans-[PtCl2(PPh3){NH(Bu)CH2Ar}], where the dimension of the Ar residue in the secondary amines has been varied from small phenyl to large pyrenyl group. The obtained complexes, tested in vitro towards a panel of human tumor cell lines showed an interesting antiproliferative effect on both cisplatin-sensitive and -resistant cells. For the most cytotoxic derivative 2a the investigation on the mechanism of action highlighted the ability to induce apoptosis on resistant cells and interestingly, to inhibit the catalytic activity of topoisomerase II.

Keywords: Antiproliferative activity; DNA topoisomerases; Transplatinum(II) complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amines / pharmacology
  • Amines / toxicity
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Flow Cytometry
  • HeLa Cells
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Organoplatinum Compounds / chemical synthesis*
  • Organoplatinum Compounds / pharmacology*
  • Organoplatinum Compounds / toxicity
  • Structure-Activity Relationship

Substances

  • Amines
  • Ligands
  • Organoplatinum Compounds