Pt(IV) Complexes in the Search for Novel Platinum Prodrugs with Promising Activity.

Abstract

The kinetically inert, six coordinated, octahedral Pt(IV) complexes are termed dual-, triple-, or multi-action prodrugs based on the nature of the axially substituted ligands. These ligands are either inert or biologically active, where the nature of these axial ligands provides additional stability, synergistic biological activity or cell-targeting ability. There are many literature reports from each of these classes, mentioning the varied nature of these axial ligands. The ligands comprise drug molecules such as chlorambucil, doxorubicin, valproic acid, ethacrynic acid, biologically active chalcone, coumarin, combretastatin, non-steroidal anti-inflammatory drugs (NSAIDs) and many more, potentiating the anti-proliferative profile or reducing the side effects associated with cisplatin therapy. The targeting and non-targeting nature of these moieties exert additive or synergistic effects on the anti-cancer activity of Pt(II) moieties. Herein, we discuss the effects of these axially oriented ligands and the changes in the non-leaving am(m)ine groups and in the leaving groups on the biological activity. In this review, we have presented the latest developments in the field of Pt(IV) complexes that display promising activity with a reduced resistance profile. We have discussed the structure activity relationship (SAR) and the effects of the ligands on the biological activity of Pt(IV) complexes with cisplatin, oxaliplatin, carboplatin and the Pt core other than approved drugs. This literature work will help researchers to get an idea about Pt(IV) complexes that have been classified based on the aspects of their biological activity.