Kinetically Inert Platinum (II) Complexes for Improving Anticancer Therapy: Recent Developments and Road Ahead

Abstract

The search for better chemotherapeutic drugs to alleviate the deficiencies of existing platinum (Pt) drugs has picked up the pace in the millennium. There has been a disparate effort to design better and safer Pt drugs to deal with the problems of deactivation, Pt resistance and toxic side effects of clinical Pt drugs. In this review, we have discussed the potential of kinetically inert Pt complexes as an emerging class of next-generation Pt drugs. The introduction gives an overview about the development, use, mechanism of action and side effects of clinical Pt drugs as well as the various approaches to improve some of their pharmacological properties. We then describe the impact of kinetic lability on the pharmacology of functional Pt drugs including deactivation, antitumor efficacy, toxicity and resistance. Following a brief overview of numerous pharmacological advantages that a non-functional kinetically inert Pt complex can offer; we discussed structurally different classes of kinetically inert Pt (II) complexes highlighting their unique pharmacological features.

Keywords: Antitumor; Kinetic inertness; Nephrotoxicity; Platinum drugs; Platinum resistance.