The unquestionable therapeutic success of the anticancer drug cisplatin and
its second and third generation analogues has triggered, during the past fifty years, the
development of several metal-based potential chemotherapeutic agents, most of which
have unfortunately failed to enter clinical trials. In this context, since the late 1990s, the
Biomedicinal Chemistry Research Group at the University of Padova (Italy) 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 reduced side-effects.
Among all, some selected gold(III) complexes have been showing outstanding in vitro
and in vivo antitumor properties and negligible (or even no) acute and renal toxicity,
compared to the reference clinically-established platinum drugs.
Starting from the rationale behind such investigations, results achieved to date are here
summarized, focusing on the in-depth mechanistic studies that have been providing
insights into the mechanism of action of this class of metal compounds. New prospects
opened up by these anticancer agents, including the latest development of “second
generation” gold-based peptidomimetics for the targeted chemotherapy, are also
illustrated and discussed.
Keywords: Gold, dithiocarbamate, anticancer activity, metallodrug, proteasome
inhibitor, nephrotoxicity, peptidomimetic, drug delivery, targeted chemotherapy.
