Therapeutic potential of peroxynitrite decomposition catalysts: a patent review

Peroxynitrite is a cytotoxic oxidant species implicated in a host of pathologies, including inflammatory and neurodegenerative diseases, cancer, radiation injury and chronic pain. With the recognition of the role of peroxynitrite in disease, numerous experimental and therapeutic tools have arisen to probe peroxyntirite's pathophysiological contribution and attenuate its oxidative damage. Peroxynitrite decomposition catalysts (PNDCs) are redox-active compounds that detoxify peroxynitrite by catalyzing its isomerization or reduction to nitrate or nitrite.

This review discusses recent research articles and patents published 1995 - 2014 on the development and therapeutic use of PNDCs. Iron and manganese metalloporphyrin PNDCs attenuate the toxic effects of peroxynitrite and are currently being developed for clinical applications. Additionally, some Mn porphyrin-based PNDCs have optimized pharmaceutical properties such that they exhibit greater peroxynitrite selectivity. Other classes of PNDC agents, including bis(hydroxyphenyl)dipyrromethenes and metallocorroles, have demonstrated preclinical efficacy, oral availability and reduced toxicity risk.

Interest in the drug-like properties of peroxynitrite-neutralizing agents has grown with the realization that PNDCs will be powerful tools in the treatment of disease. The design of compounds with enhanced oral availability and peroxynitrite selectivity is a critical step toward the availability of safe, effective and selective redox modulators for the treatment of peroxynitrite-associated pathologies.