Platinum(IV) and platinum(II) anticancer complexes with biologically active releasable ligands

The concept of multi-action octahedral platinum(IV) complexes is based on the rational derivatization of anticancer square-planar platinum(II) compounds (e.g., cisplatin or oxaliplatin) by a bioactive axial ligand(s) bearing its own biological effect. Over the years, many multi-action Pt(IV) complexes have been reported to exhibit an extraordinarily high anticancer effect both in vitro and in vivo, and, importantly, to kill cancer cells through a unique mechanism of action (MoA), combining effects of parent Pt(II) species and released bioactive ligand(s). In this review article, we summarized the structural types of Pt(IV) complexes reported to date in the literature, and these complexes were categorized according to various criteria - the parent Pt(II) complex, the number and type of bioactive ligands, type of the second (either bioactive or innocent) axial ligand, and nuclearity (homometallic and heterometallic Pt(IV) complexes are involved). Most of the multi-action Pt(IV) complexes reported so far include carboxylates as axial ligands, and they are classified among bis(carboxylato) complexes, mono(carboxylato) complexes with hydroxide/chloride or a different group as the other axial ligand. A smaller group is represented by non-carboxylato complexes, which involve carbonato, carbamato or thiocarbonato groups as well as N-donor amides or heterocycles (e.g., pyridine). For the first time, we involved multi-action Pt(II) complexes releasing bioactive Pt(II) species and bioactive ligand(s) as well, which allowed also a critical comparison of the two structural types (i.e., multi-action Pt(IV) complexes vs. multi-action Pt(II) complexes). Special attention is paid to the discussion of solution behaviour, activation towards the release of a bioactive ligand(s) and biological activity of the reviewed types of Pt complexes. A relevant comparison of these crucial features of multi-action Pt complexes is beneficial for future development of these pharmacologically highly prospective compounds.