Cytotoxic properties of platinum(IV) and dinuclear platinum(II) complexes and their ligand substitution reactions with guanosine- 50-monophosphate

Abstract

The substitution reaction of the Pt(IV) complex [PtCl4(bipy)] with guanosine-50-monophosphate (50-GMP) was studied by UV-Vis spectrophotometry. This reaction was investigated under pseudo-first-order conditions at 37 °C in 25 mMHepes buffer (pH = 7.2) in the presence of 10 mM NaCl to prevent the hydrolysis of the complex. The substitution of chlorides in [{trans-Pt(NH3)2Cl} 2(l-1,2- bis(4-pyridyl)ethane)](ClO4)2 (Pt3) complex by 50-GMP was followed by 1H NMR spectroscopy under second-order conditions. Very similar values for the rate constants of both substitution steps were obtained. The Pt(IV) complexes, [PtCl4(bipy)] and [PtCl4(dach)], as well as dinuclaer Pt(II) [{trans-Pt(NH3)2Cl}2(l-pyrazine)](ClO4)2 (Pt1), [{trans- Pt(NH3)2Cl}2(l-4,40- bipyridyl)](ClO4)2 - DMF (Pt2) and [{trans-Pt(NH3)2Cl}2(l-1,2-bis(4-pyridyl) ethane)](ClO4)2 (Pt3) complexes, displayed potent cytotoxic activity against human ovarium carcinoma cell line TOV21G and lower activity toward human colon carcinoma HCT116 cell line at the same concentrations. Our data indicate that these platinum complexes could be explored further, as potential therapeutic agents for ovarian cancer. © Springer Science+Business Media B.V. 2012.