Copper pyrithione complexes with endoplasmic reticulum localisation showing anticancer activity via ROS generation

Copper complexes have great potential to overcome the disadvantages of platinum-based anticancer agents, owing to their lower systemic toxicity. Copper pyrithione showed early promise as an anticancer candidate, but further studies have not been forthcoming. Herein, we report a series of copper pyrithione derivatives that show between 1 and 2 orders of magnitude higher activity than cisplatin against pancreatic and breast cancer cell lines, along with good selectivity over healthy cells. Reactive oxygen species (ROS) generation is determined to be a likely mode of action. A fluorescent analogue shows localisation in the endoplasmic reticulum of cells, which is highly unusual for metal-based therapeutics and opens up the potential for unique modes of therapeutic action.