Platinum iodido complexes: A comprehensive overview of anticancer activity and mechanisms of action

Platinum iodido complexes have long been recognized as synthetic intermediates of various platinum complexes (e.g., chlorido or carboxylato), including the world-wide used platinum-based anticancer drugs cisplatin, carboplatin and oxaliplatin. At the same time, platinum iodido complexes have been overlooked by bioinorganic chemists, because several pioneer works deemed the iodido ligand as unsuitable for the development of novel platinum-based metallotherapeutics. This was because most of platinum iodido complexes were identified as biologically and pharmacologically non-prospective as compared with the chlorido analogues. More recently, several research teams have developed various types of platinum iodido complexes as substances possessing the combination of promising chemical, physical, and especially biological properties. In particular, a number of platinum iodido complexes showed higher activity than their chlorido analogues and they exceeded even the activity of the conventional platinum-based drugs. Additionally, a lot of results have implied that relevant differences exist in the mechanism of action between platinum iodido agents, and their chlorido analogues and clinically-used platinum complexes. Herein, we offer a comprehensive overview of anticancer active platinum iodido complexes, together with the most relevant aspects of their mechanisms of action. We focused on all the structural types, differing in the platinum oxidation state, nuclearity, number of iodido ligands and type/s of donor atoms of the non-iodido ligands involved in the inner coordination sphere. The profound differences in the mechanisms of interactions of platinum(II) iodido complexes with biomolecules have been identified in contrast to the clinically used platinum-based metallotherapeutics. The platinum(IV) diiodido complexes represent the inactive prodrugs photoactivable to the active platinum(II) species. In addition, a number of organometallic and multinuclear platinum iodido complexes were identified among the most active agents. The reviewed platinum iodido complexes offer such unique features that they might fuel the design of novel, highly active, more specific and safer potential platinum-based therapeutics.