Copper ionophores to induce selective cuproptosis of cancer cells

Cancer therapies suffer from severe off-target effects because most of them target critical aspects of cells that are generally shared by all rapidly proliferating cells. The development of new effective therapies should aim to reduce side effects, increasing the selectivity of the administrated drugs [1]. In addition, these agents should overcome cancer cell resistance and target cancer stem cells. Some copper ionophores have shown promise in this direction thanks to an intrinsic selectivity in preferentially inducing cuproptosis of cancer cells compared to normal cells. Cuproptosis defines Cu-dependent cytotoxicity with a unique mechanism leading to cell death. In this context, we studied systems that could act as prodrugs.