title: Dicarboxylate platinum(II) complexes as inhibitors of plasma membrane H(+)-ATPase in the yeast Saccharomyces cerevisiae.
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.
authors.affiliation: Institute of Microbiology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Obłak
authors.forename: Tadeusz M
authors.initials: TM
authors.lastname: Lachowicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Waszkiewicz
authors.forename: Janina
authors.initials: J
authors.lastname: Kuduk-Jaworska
mesh_terms: D016190:Carboplatin / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005029:Ethylenediamines / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D005029:Ethylenediamines; D009944:Organoplatinum Compounds; D011522:Protons; C031234:ethylenediamine; D016190:Carboplatin; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; D005947:Glucose