Developing ROS Scavenging Agents for Pharmacological Purposes: Recent Advances in Design of Manganese-Based Complexes with Anti-Inflammatory and Anti-Nociceptive Activity

Reactive oxygen and nitrogen species, which are normal products of cell metabolism, may play a dual beneficial/deleterious role, depending on local concentration and mode of generation. As such, they have been identified as key pathogenic factors for many inflammatory and degenerative disorders, carcinogenesis, nociception and ageing. In this perspective, low molecular weight transition metal complexes with organic ligands have been and are still viewed as promising pharmaceutical agents with antioxidant/free radical scavenging properties, owing to their ability to interact and/or react with reactive oxygen or nitrogen species and counterbalance excessive endogenous free radical generation in biological systems. Among these compounds, manganese(II/III) complexes have resulted effective as ROS scavengers both in vitro and in vivo. In particular, Mn-III complexes with porphyrins and salen derivatives as well as Mn-II complexes with macrocyclic pentaamines and polyamine-polycarboxylic acids have been recently analyzed as ROS scavengers for therapeutic purposes. In this article, we summarize the chemical and biological properties of manganese complexes with low molecular weight synthetic ligands as scavengers of pro-oxidant species, with particular attention to the mechanisms operating at the metal center in the scavenging process. A proper design of the organic scaffolds may yield manganese complexes capable to catalyze different scavenging reactions, including superoxide and/or hydrogen peroxide dismutation and peroxynitrite decomposition. These manganese complexes can be viewed either as a novel class of drugs helpful to reduce oxidative tissue injury or as useful tools to get further light on the role played by ROS in biological systems.