The Influence of the Nature of the Ligand on the Antitumor Activity and Cytotoxic Effect of Binuclear Dinitrosyl Iron Complexes

Abstract

The influence of the nature of the ligands of nitric oxide-generating compounds, such as binuclear dinitrosyl iron complexes containing glutathione or mercaptosuccinate, on their tumor growth-inhibiting and cytotoxic effects has been studied in vivo and in vitro. The antitumor effect of the complex with glutathione exceeds that exerted by the complex with mercaptosuccinate. These complexes inhibit tumor growth (Lewis lung carcinoma) by 90 and 65%, respectively, compared to the control. These complexes are weakly cytotoxic against the MCF-7 human cancer cell line. The half-maximum inhibitory concentration of the complex with mercaptosuccinate at which the survival of cells is reduced by 50% (IC₅₀) is 0.8 μmol/mL (640 μg/mL), whereas in the case of the complex with glutathione it is 2 μmol/mL (1600 μg/mL). It is assumed that the antitumor activity of iron complexes is determined by their ability to enter immunocompetent cells, which provide a direct route to tumor tissues.