The design of cobalt(III) complexes of phenazine-1-carboxamides as prointercalators and potential hypoxia-selective cytotoxins

A series of cobalt (III) complexes, [Co(Racac)(2)(L)](+), have been prepare d as potential hypoxia-selective prointercalator forms of the ligands L, wh ere L is the cytotoxic DNA monointercalating ligands N-[2-[(aminoethyl)amin o]ethyl]-phenazine-1-carboxamide and N-[5-[(aminoethyl)amino]pentyl]-phenaz ine-1-carboxamide or the potentially bis(intercalating) ligand bis[2-(phena zine-1- carboxamido)ethyl]-1,2-diaminoethane. The cobalt(III) complexes of the monointercalating ligands have significantly lower DNA binding affinity and cytotoxicity than the ligands themselves, indicating the potential uti lity of this prodrug approach for deactivation land release under hypoxic c onditions). However, the complexes showed only low hypoxic selectivity. The complex of the bis(intercalating) ligand also showed significantly lower D NA binding affinity than the free ligand, but in this case there was no att enuation of cytotoxicity.