Steps forwards to a new type of oncotherapy: from the solution chemistry of Au(III)-dithiocarbamato complexes to the design and development of innovative Au(III)- and Cu(II)-based cancer-targeting agents

In order to overcome the side effects of the chemotherapy, but remaining firmly convinced in the powerful role of the medicinal inorganic chemistry, Fregona's research group, since 2000, developed a series of metal-based dithiocarbamato molecules, in particular containing Au(III), Ru(III) and Cu(II) metal centers, which are highly active in vitro toward a great number of human tumor cell lines and less toxic in vivo, compared to other chemotherapeutics. Although several insights into the chemistry of these powerful coordination compounds were performed in last years, some aspects remain to be elucidating. In the first part of this work, we present a comprehensive study concerning the synthesis, the characterization and the solution behavior of eight Au(III) dithiocarbamato complexes, revealing their peculiar and fascinating chemistry. Moreover, seven of them showed interesting biological properties in vitro toward a selected human tumor cell line. The second part of the Ph.D. research was focused on the synthesis, characterization and biological evaluation of novel bio-conjugated Au(III) and Cu(II) complexes with the aim of improve the accumulation of the anticancer metal payload into malignant cells. In order to reach this goal, three different cancer-targeting agents were chosen and, on the whole, nine different complexes were synthetized and tested as anticancer agents. Intriguingly, one of them proved a high cytotoxic activity toward a selected human tumor cell line, paving the way to future studies investigating the role of the cancer-targeting functionalization in the selective targeting of the complex toward cancerous tissues.