Platinum(IV)-based prodrugs as an alternative to Pt(II)-based drugs: synthesis and biological action

The chemotherapy with cisplatin and its analogues widely used in medical practice is associated with undesirable side effects caused by non-selective ligand exchange and binding of the complexes to various biomolecules in the body. An alernative to classical platinum(II)-based drugs are platinum(IV) prodrugs, that is, platinum(II) complexes additionally modified with diverse biologically active axial ligands, including known pharmaceutical products. In recent years, quite a few studies devoted to the design of effective Pt(IV) prodrugs have been published, with some of the developed agents being markedly superior to clinically used cisplatin and carboplatin in therapeutic efficacy. This review summarizes the synthetic approaches to the design of Pt(IV) prodrugs and modification of the axial ligands. The second part of the review is devoted to the biological activity of Pt(IV) prodrugs reported in the period from 2018 to 2023 and comparison of various approaches to the design of effective anticancer agents based on these compounds. The bibliography includes 239 references.