Next-Generation Anticancer Metallodrugs

Seiji      Komeda; Angela      Casini

Abstract

More than 99% of currently approved clinical drugs are organic compounds. In contrast, the percentage of metal-containing drugs (metallodrugs) is very low. In cancer chemotherapy, however, platinum coordination compounds represented by cisplatin and derivatives thereof are essential anticancer agents with proven effects against a variety of tumors. Because of the proven clinical applications of these platinum-based drugs, the number of research initiatives to identify other metallodrugs that can be used for cancer therapy has increased considerably in the field of inorganic biochemistry. Anticancer platinum compounds continue to be designed and synthesized through several different approaches in order to improve the therapeutic effects and to overcome the disadvantages of current platinum-based drugs. The use of transition metal compounds other than platinum has also attracted attention. Gold coordination complexes, for instance, demonstrate outstanding cytotoxic properties, and certain ruthenium complexes possess a strong ability to inhibit metastases of solid invasive tumors. In this review, the potential of anticancer metallodrugs is described and representative examples from the most recent families of Pt-, Ru-, and Au-based compounds are discussed with respect to their possible modes of action and most probable biomolecular targets.

Keywords: Metallodrugs, cancer, nucleic acids, protein targets, clinical drugs, organic compounds, cancer chemotherapy, inorganic biochemistry, ruthenium complexes possess, biomolecular targets, platinum electrodes, high therapeutic efficacy, antitumor-active Pt(II) complexes, Cisplatin-resistant cells