Redox Activation as Strategy for the Development of New Drugs Applied to the Cancer Treatment

Abstract

Redox activation has been exploited in the development of drugs for treatment of several diseases, including cancer. Some cancers generate solid tumors that have a poor vascularization, which leads to the generation of hypoxic environments, which in turn, limit the effectiveness of both radio and chemotherapies. These regions have a higher reducing capability when compared to normoxic tissues. Thus, substances capable of circulating intact through the body can be reduced and activated selectively in the hypoxic region of the tumor, becoming cytotoxic. Based on this strategy, five classes of Prodrugs Activated by Hypoxia (PDAHs) are described and include nitro(hetero)cycles (p. eg. nitrogen mustards and nitroimidazoles), aromatic N-oxides, aliphatic Noxides, quinones and transition metal complexes. In this review, some advances in the development of PDAHs are discussed, focusing on the relationship between the redox properties and biological activity.