In vitro antigenotoxicity of novel heterometallic dinuclear complexes

Abstract

The four novel dinuclear complexes [{cis-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpy-Cl)}](ClO4)2, [{trans-PtCl(NH3)2(μ-4,4′-bipyridyl)ZnCl(terpy-Cl)}](ClO4)2, [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy-Cl)}](ClO4)2 and [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy-Cl)}](ClO4)2, derived from mononuclear [ZnCl(terpy-Cl)], (where terpy-Cl = 4’-chloro-2,2′:6′,2′′-terpyridine) were synthesized and characterized. The possible DNA-protective effects of these complexes at different concentrations (25, 50, 100, 200, and 400 μg/ml) against hydroxyl and peroxyl radicals-induced DNA damage were determined using two in vitro antioxidant assays. Compared with the negative and positive controls, all complexes showed the significant DNA-protective effects at the concentrations tested, indicating scavenging activity on hydroxyl and peroxyl radicals generated by FeSO4, H2O2, and AAPH. In our previous study four dinuclear complexes of similar structure, analogues of these complexes but without chloride substituent in terpy ligand, were also used to evaluate the antigenotoxicity. Only [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy)}](ClO4)2 had significant dose-dependent ability to inhibit peroxyl as well as hydroxyl radicals which is in line with the current study and antigenotoxicity of tested complex [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpy-Cl)}](ClO4)2. The significant DNA protective potential against hydroxyl and peroxyl radicals was also obtained for the remaining three tested dinuclear complexes. The presence of the chloride in the structure of newly synthesized complexes increase the electronic density on Zn center and, thus, decrease its nucleophilicity, which could be an explanation of their behavior. This data could be useful for further in vitro and in vivo biological evaluations of these antioxidative compounds.