Copper Complexes as Anticancer Agents

Following the great impetus provided by the discovery of the anticancer activity of cisplatin [cis-diamminedichloridoplatinum(II)] in the 1960s, extensive search for alternative metal-based drugs with improved pharmacological properties has been attempted. Actually, the outstanding efficacy showed by clinically approved Pt(II) compounds is counterbalanced by severe toxic effects on normal tissues, and by the early appearance of drug resistance phenomena. Among non-Pt compounds, copper complexes are considered promising alternatives to platinum drugs as antitumor agents. In particular, the discovery of significant alterations in cancer cell copper metabolism and the different responses to copper between normal and tumor cells have paved the way for the development of copper-based anticancer drugs. This article aims to summarize the extant literature on the most well-studied classes of anticancer copper complexes, with special emphasis on research performed in the last 10 years, most relevant to the elucidation of the involved mechanisms of action and/or reporting on in vivo efficacy evaluations.