Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

Department of Chemical and Geological Sciences University of Cagliari 09042 Cagliari Italy

Department of Chemistry Faculty of Science Masaryk University 62500 Brno Czech Republic

Department of Histology and Embryology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital 65691 Brno Czech Republic

Research Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute 65653 Brno Czech Republic

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