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Developing ROS scavenging agents for pharmacological purposes: recent advances in design of manganese-based complexes
1Department of Anatomy, Histology & Forensic Medicine, University of Florence, V.le G.Pieraccini, 6 - I-50139 Firenze, Italy.
Abstract:
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.
Insights
Manganese complexes effectively scavenge reactive oxygen species (ROS), offering potential therapeutic benefits for oxidative stress-related diseases. These compounds show promise in reducing tissue injury and understanding ROS roles.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Pharmacology
Background:
- Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are metabolic products with dual roles, implicated in inflammatory, degenerative, carcinogenic, and aging processes.
- Low molecular weight transition metal complexes with organic ligands are investigated for antioxidant and free radical scavenging properties.
- Manganese complexes, particularly Mn(III) and Mn(II) variants, have demonstrated efficacy in scavenging ROS both in vitro and in vivo.
Purpose of the Study:
- To summarize the chemical and biological properties of manganese complexes with synthetic ligands as scavengers of pro-oxidant species.
- To highlight the mechanisms of ROS scavenging at the metal center.
- To explore the therapeutic potential of these manganese complexes in reducing oxidative tissue injury.
Main Methods:
- Review of literature on manganese complexes with porphyrins, salen derivatives, macrocyclic pentaamines, and polyamine-polycarboxylic acids.
- Analysis of chemical structures and biological activities of selected manganese complexes.
- Investigation of reaction mechanisms for ROS scavenging, including dismutation and decomposition.
Main Results:
- Manganese complexes, especially Mn(III) with porphyrins/salen and Mn(II) with macrocycles/polyamines, are effective ROS scavengers.
- Designed organic scaffolds enable manganese complexes to catalyze superoxide dismutation, hydrogen peroxide dismutation, and peroxynitrite decomposition.
- These complexes demonstrate significant antioxidant activity in biological systems.
Conclusions:
- Manganese complexes represent a promising class of therapeutic agents for mitigating oxidative tissue damage.
- Tailored manganese complexes can be designed to target specific ROS and RNS.
- These compounds serve as valuable tools for elucidating the role of ROS in biological systems and disease pathogenesis.
