Copper(II) complexes as potent chemotherapeutic agents for anticancer therapy

Cancer is the second top leading cause of death worldwide. According to WHO, approximately 10 million individuals died of cancer in 2022, and this number is expected to rise to 16.4 million by 2040. Since the FDA approval of cisplatin as a chemotherapeutic drug for cancer treatment in 1978 and its second generations of carboplatin in 1989 and oxaliplatin in 2002, large number of platinum-based derivatives have been developed, but none of them have been entirely successful in treating this fatal disease. Despite the extensive use of these chemotherapeutic agents in clinical oncology and their widespread application, these agents often exhibit severe side effects such as neurotoxicity, nephrotoxicity, ototoxicity, reduced immunity, gastrointestinal disorders, kidney, and liver failure, as well as tumor resistance to cisplatin limit the use of these drugs and specifically cisplatin. These challenges raise the urgent need for the development of alternative chemotherapeutic agents. Copper complexes have emerged over the last two decades as more effective anticancer agents with possible better pharmacological profiles. The cytotoxicity of many Cu(II/I) compounds have been reported in vitro and in vivo cancer cells and reveal high potent cytotoxicity. These include mono- and di-nuclear Cu(II) complexes derived from compounds bearing pyridyl rings, terpyridyl derivatives (R-TPY)  as well as tripodal tetradentate amines incorporating pyridyl and phenolate moieties. The in vitro anticancer activity of these compounds was demonstrated against a wide range of human cancer cell lines.  For example, the binuclear doubly bridged pyridyl-phenoxido Cu(II) complexes revealed significant antiproliferative activity with the highest cytotoxic selectivity index (SI > 10) against A2780 (ovarian cancer)¹ and even better results were obtained with m-MeO-TPY in MCF-7 (breast cancer).² The mechanism of action of the Cu(II) compounds against cancer cells are addressed.

Dr. Salah Massoud published more than 200 papers in peer-reviewed journals on copper as anticancer agents, and DNA cleavage and ATP hydrolysis by transition metal complexes, Single molecule magnets in Co(II) and lanthanides, molecular magnetism in polynuclear coordination compounds as well as fluorescence in lanthanides. He delivered more than 200 articles as invited speakers to National and International Conferences and several schools around the world. He holds a Ph.D. from Boston University, USA in bioinorganic and inorganic chemistry and obtained the  M.Sc. and B.Sc. from Alexandria University. He serves in the editorial board and guest editor for several journals. He is currently a Distinguished Professor at University of Louisiana, USA and Alexandria University, Egypt.