Copper Complexes of Bioactive Ligands with Superoxide Dismutase Activity

Abstract

Free radicals or reactive oxygen species (ROS) are highly toxic and their damaging effects result in a variety of detrimental health issues such as neurodegenerative, cardiovascular and age-related diseases. Human body has evolved an effective defense system including superoxide dismutase (SOD) and catalase against the toxicity of these free radicals. SOD is a metalloenzyme and it acts as an excellent antioxidant to protect the body from superoxide radicals that are generated in the biological system. However, the clinical use of SOD is limited due to its short in vivo life span, and its large size that hampered its penetration across the cell membranes. Pharmaceuticals that provide ROS scavenging systems are the most effective when the production of ROS exceeds the scavenging capacity of endogenous SOD as a result of aging or pathological processes. Inspired by the Nature, scientists have designed metal-based mimics of the superoxide dismutase. This review focuses on different copper complexes that are developed from bioactive ligands and mimic the protecting action of the SOD.

Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione

“…Notably, removal of superoxide by the Cu(II)-GSSG complex was estimated to take place at a rate constant (k Cu(II)-GSSG ) of 7.8 × 10 6 M −1 s −1 , which highly compares with the one reported by Jouini et al [104] (6 × 10 6 M −1 s −1 ). Although the latter value is three orders of magnitude lower than that reported for superoxide dismutase (SOD; 2 × 10 9 M −1 s −1 [110]), it is totally comparable to or even greater than the rate constant values reported for several other copper-containing complexes with SOD mimetic properties; for instance, for those formed between Cu(II) and various amino acid residues and peptides [111], salicylates [112,113], semicarbazones [114][115][116], macrocyclic- [117] and tetradentateSchiff-bases [118,119].…”

Metal complexes in cancer therapy – an update from drug design perspective

“…The role of copper in angiogenesis has been a subject of controversy; generally, the role of metals in this process is still under scrutiny 55. However, copper complexes are known to mimic superoxide dismutase (SOD),56 an important antioxidant enzyme that protects cells from harmful radical superoxide through its dismutation to nontoxic molecules 56. They are present in almost all living organism 56.…”

“…However, copper complexes are known to mimic superoxide dismutase (SOD),56 an important antioxidant enzyme that protects cells from harmful radical superoxide through its dismutation to nontoxic molecules 56. They are present in almost all living organism 56. The native SOD is a natural scavenger of free radicals that work very efficiently in the body;56 therefore, in the presence of an imbalance between the generation of free radicals and the concentration of dismutation enzymes,56 a low molecular weight mimic of antioxidant enzymes, especially SOD, with good scavenging activity is required 56.…”

“…They are present in almost all living organism 56. The native SOD is a natural scavenger of free radicals that work very efficiently in the body;56 therefore, in the presence of an imbalance between the generation of free radicals and the concentration of dismutation enzymes,56 a low molecular weight mimic of antioxidant enzymes, especially SOD, with good scavenging activity is required 56. Copper complexes, particularly of a low molecular weight, are indicated, since they are good mimics of SOD.…”

Cu AND Mn COMPLEXES OF NICOTINIC ACID AND IMIDAZOLE: A CURRENT REVIEW.

“…This coordination complex characterized by crystallographic and spectroscopic method. By applying xanthine-xanthine oxidase assay, SOD (superoxide dismutase activity) of the complex was determined [50].…”