Metallo-Drugs in Cancer Therapy: Past, Present and Future

Abstract

Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. For these reasons, the identification of new drug designs and therapeutic strategies that could target cancer cells while leaving normal cells unaffected still continues to be a challenge. Despite advances that have led to the development of new therapies, treatment options are still limited for many types of cancers. This review provides an overview of platinum, copper and ruthenium metal based anticancer drugs in clinical trials and in vitro/in vivo studies. Presumably, copper and ruthenium complexes have greater potential than Pt(II) complexes, showing reduced toxicity, a new mechanism of action, a different spectrum of activity and the possibility of non-cross-resistance. We focus the discussion towards past, present and future aspects.

Keywords: cancer; copper; metal complexes; platinum; ruthenium.

Figure 1

Chemical structures of cisplatin and its derivatives.

Figure 2

Chemical structure of BBR 3464.

Figure 3

Chemical structure of: (a) Satraplatin; (b) Picoplatin.

Figure 4

Chemical structure of: (a) Ormaplatin; (b) Iproplatin.

Figure 5

Chemical structure of: (a) Elesclomol; (b) Complex Cu(II)-Elesclomol.

Figure 6

Chemical structure of Casiopeinas: (a) Casiopeina III; (b) Casiopeina II-gly.

Figure 7

Chemical structure of NAMI-A.

Figure 8

Chemical structure of KP1019 and of it’s sodium salt, KP1339.