Chalcoplatin, a dual-targeting and p53 activator-containing anticancer platinum(iv) prodrug with unique mode of actionElectronic supplementary information (ESI) available. See DOI: 10.1039/c4cc10409a

Complexation of cisplatin with a p53 activator as a single anticancer agent resulted in synergistically improved cytotoxicity in p53 wild-type but not p53 null human cancer cells. Mechanistic investigation was carried out on this dual-targeting Pt( iv ) prodrug, chalcoplatin. The prodrug effectively entered cancer cells and arrested the cell cycle at the S and G 2 /M phases, distinctive of that from cisplatin. Chalcoplatin significantly induced p53 activation as well as the subsequent apoptosis pathways. This unique mode of action renders chalcoplatin remarkably cytotoxic and makes this compound among the first examples of a Pt( iv ) prodrug that directly interacts with the downstream pathway after the formation of Pt-DNA lesions. Killing two birds with one stone: a p53 activator was conjugated with cisplatin as a single anticancer agent, leading to synergistically improved cytotoxicity.