Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid Metabolism

Abstract

The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics.

Figure 1

Chemical structures of cisplatin [cis-diamminedichloroplatinum(II)], LA-9 [(SP-4-3)-(1-adamantylamine)amminedichloroplatinum(II)], and LA-12 [(OC-6-43)-bis(acetato)(1-adamantylamine) amminedichloroplatinum(IV)].

Figure 2

A diagram depicting potential innovative chemotherapy strategies which might be employed to increase efficacy of novel platinum(IV) complexes.