Copper(II) cyclopeptides with ROS-mediated high cytotoxicity

We have synthesized two bipyridyl-based oligocationic cyclopeptides through solid phase peptide synthetic methods (SPPS) and studied their metal-binding, redox and biological properties in the presence of copper(II) ions in water media by several techniques. Remarkably, the studies performed indicate that, while the free cyclopeptides exhibit quite low or at most discrete cytotoxic properties, their Cu(II) derivatives show very high cytotoxic effects (an order of activity higher than cisplatin!) against different cancer cells lines, and, importantly, that the reason for this activity is that they can efficiently generate ROS within the cellular environment