Cu-ligand complexes as anticancer agents

Copper is an essential trace element in humans and therapeutic approaches based on the interaction of synthetic ligands with Cu attracted considerable medicinal interest. For instance, Cu-ligand complexes (Cu-L) are intensively investigated as anticancer agents. An often-implicated mechanism of cytotoxicity in cancer cells is the increased production of reactive oxygen species catalysed by the Cu-L. This can occur in the presence of native reductants, such as ascorbate or glutathione (GSH), under aerobic conditions. Based on the literature and our recent results, the lysosome might be an important place of action for these Cu-L. Moreover, the GSH oxidation by Cu-phenanthroline complexes increased at lower pH, such as the typical lysosome value 5. Therefore, the present project aims to understand why the catalytic activity increases at lower pH. This is of fundamental interest as thiol reactivity normally drops with pH and this finding could be of importance in the anticancer mechanism.