| Abstract
| - The compounds [Pt(Me2phen)(acy)2](NO3)2 (1), [Pt(Me2phen)(pen)2](NO3)2, [Pt(phen)(acy)2](NO3)2(2), and [Pt(phen)(pen)2](NO3)2, containing the bidentate 1,10-phenanthroline (phen) or 2,9-dimethyl-1,10-phenanthroline (Me2phen, neocuproine) and the antiviral agents acyclovir (acy)or penciclovir (pen), show different in vitro toxicity, the Me2phen complexes being appreciablymore toxic than the phen complexes. To explain the different behavior, we investigated thereaction of complexes 1 and 2 with glutathione (γ-glutamylcysteinylglycine, GSH), a peptidebelieved to play an important role in driving the cellular effects of platinum drugs. The reactionled to different products, the phen complexes forming a stable binuclear μ-thiol-bridged speciesstill containing the phenanthroline and the Me2phen complexes releasing the neocuproine ligandand forming an insoluble material. In vitro tests confirmed that the greater cell toxicity ofcomplex 1 is due to the displacement of the neocuproine ligand by GSH. The results highlightthe great dependence of the glutathione reactivity upon relatively small changes in the platinumcoordination sphere.
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