Dinuclear Iron Complexes of Iminopyridine-Based Ligands as Selective Cytotoxins for Tumor Cells and Inhibitors of Cancer Cell Migration

A family of dinuclear iron (II) compounds with iminopyridine-based ligands displays selective cytotoxic activity against cancer cell lines. All compounds have IC₅₀ values 2-6 fold lower than that of cisplatin, and 30-90 fold lower than that of carboplatin for the tumor cell lines assayed. Comparing the IC₅₀ values between tumor and non-tumor cell lines, the selectivity indexes range from 3.2 to 34, compound 10, [Fe₂(4)₂(CH₃CN)₄](BF₄)₄, showing the highest selectivity. Those compounds carrying substituents on the iminopyridine ring show the same cytotoxicity as those without substituents. However, the electronic effects of the substituents on position 6 may be important for the cytotoxicity of the complexes, and consequently for their selectivity. All compounds act over DNA, promoting cuts on both strands in the presence of reactive oxygen species. Since compound 10 presented the highest selectivity, its cytotoxic effect was further characterized. It induces apoptosis, affects cell cycle phase distribution in a cell-dependent manner, and its cytotoxic effect is linked to reactive oxygen species generation. In addition, it decreases tumor cell migration, showing potential antimetastatic effects. These properties make compound 10 a good lead antitumor agent among all compounds studied here.