The unquestionable therapeutic success of the anticancer drug cisplatin and its second- and third-generation analogues has triggered, in the past forty years, the development of several metal-based potential chemotherapeutic agents, most of which have failed to enter clinical trials. In this context, during the last decade, our research group has been making quite an effort to design a number of metal-dithiocarbamato derivatives that were expected, at least in principle, to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Among all, gold(III) complexes have shown outstanding in vitro and in vivo antitumour properties and reduced or no systemic and renal toxicity, compared to the reference drug. Here, we summarize the results achieved to date, focusing on the mechanistic studies and the potential future developments opened up by our research work.

Gold has always aroused great interest in the history of mankind. It has been used for thousands of years for jewelry, religious cult valuables, durable goods and in the art world. However, few know that such a precious and noble metal was exploited in the past by the ancients also for its therapeutic properties. More recently, in the twentieth century some complexes containing gold centers in the oxidation state +1 were studied for the treatment of the rheumatoid arthritis and the orally-administered drug Auranofin was approved by the FDA in 1985. From the chemical point of view, gold derivatives deserve special attention due to the unique position of this metal within the periodic table, which results in unconventional relativistic effects and, ultimately, in the highest electronegativity, electron affinity and redox potential among all metals. In this review, after an introduction concerning the use of gold complexes in medicine, we have examined all the patents internationally or nationally published in the years 2010-2015 (until December 31, 2015) and describing new inorganic compounds containing gold(I) and gold(III) with proved therapeutic properties. These patents were filed to mainly protect compounds with promising anticancer and anti-inflammatory activities (total 18 and 4, respectively). In particular, this work explores both coordination compounds containing ligands with various donor atoms (e.g., N-, O-, S- and -P) and organo-gold derivatives with at least one Au-C bond. The toxicological profile and the intracellular targets reported for some among the patented gold derivatives are discussed.

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. 53% inhibition of breast tumor growth in mice was observed after 27 days of treatment at 1.0 mg kg⁻¹ d⁻¹, compared to control. Remarkably, if only the most responsive mice are taken into account, 85% growth inhibition, with some animals showing tumor shrinkage, was observed after 13 days. These results led us to file an international patent, recognizing this class of gold(III) peptidomimetics as suitable candidates for entering phase I clinical trials.