Dicarboxylate platinum(II) complexes as inhibitors of plasma membrane H(+)-ATPase in the yeast Saccharomyces cerevisiae

Cell Mol Biol Lett. 2003;8(4):1005-11.

Abstract

A series of cytotoxic neutral dicarboxylatoplatinum(II) complexes containing D(+), L(-) or DL-malate dianion and ethylenediamine or 1-ethylimidazole as ligands were examined using ATPase activity assays and the proton extrusion test. ATPase activity assays in vitro on plasma membrane H+-ATPase and on mitochondrial ATPase were carried out. The concentrations of compounds inhibiting enzyme activity to 50 per cent (J50) was determined. The new platinum complexes showed a stronger level of inhibition of both ATPases than the reference carboplatin; this inhibitory activity is related to a stereoisomeric form of anionic platinum ligands. ATPase inhibition in vivo was tested by glucose-stimulated proton extrusion and the influence of platinum compounds on this process in yeast cells was determined. Significant differences in activity levels were observed between those complexes with 1-ethylimidazole and those with ethylenediamine.

MeSH terms

  • Carboplatin / pharmacology
  • Cell Membrane / enzymology*
  • Enzyme Inhibitors / pharmacology
  • Ethylenediamines / chemistry
  • Glucose / pharmacology
  • Hydrogen-Ion Concentration
  • Mitochondrial Proton-Translocating ATPases / antagonists & inhibitors
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Proton-Translocating ATPases / metabolism*
  • Protons
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*

Substances

  • Enzyme Inhibitors
  • Ethylenediamines
  • Organoplatinum Compounds
  • Protons
  • ethylenediamine
  • Carboplatin
  • Mitochondrial Proton-Translocating ATPases
  • Proton-Translocating ATPases
  • Glucose