Synthesis, antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes

Bioorg Med Chem. 2013 Nov 15;21(22):6965-72. doi: 10.1016/j.bmc.2013.09.025. Epub 2013 Sep 19.

Abstract

A convenient synthetic route and the characterization of complexes trans-[PtCl2(L)(PPh3)] (L=Et2NH (2), (PhCH2)2NH (3), (HOCH2CH2)2NH) (4) are reported. The antiproliferative activity was evaluated on three human tumor cell lines. The investigation on the mechanism of action highlighted for the most active complex 4 the capacity to affect mitochondrial functions. In particular, both the induction of the mitochondrial permeability transition phenomenon and an aspecific membrane damage occurred, depending on concentration.

Keywords: Antiproliferative activity; Mitochondria; Mitochondrial permeability transition; Oxidative stress; Transplatinum complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • HeLa Cells
  • Humans
  • Isomerism
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Phosphines / chemistry
  • Platinum / chemistry*
  • Platinum / pharmacology*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Phosphines
  • Platinum