Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases

Abstract

Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.

Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections

“…Physical Characteristics of Gram-negative and Gram-positive Bacteria with Relevance to Iron Uptake—It is well established that iron acquisition is critical in promoting the growth and virulence of numerous pathogenic bacteria [ 32 ]. Since antibiotic resistance is of major concern in the treatment of pathogenic bacterial-induced infections, novel treatment agents are direly needed.…”

“…Some chelators are derived from bacterial sources including Desferioxamine (also known as deferoxamine (DFO), produced by Streptomyces pilosus ) and Desferrithiocin ((DFT), a tridentate siderophore, produced by Streptomyces antibioticus ) [ 28 , 29 , 30 ]. Moreover, phytochelators, obtained from plant components including vegetables and fruits, elicit iron-chelating activities; polyphenols are one such class with the ability to chelate iron with high affinity and promote health [ 31 , 32 ]. Mammalian-derived physiological iron chelators include (1) transferrin, found in blood plasma and involved in body-wide iron transport and (2) lactoferrin, enriched in neutrophils and in bodily secretions [ 32 , 33 , 34 ].…”

“…Moreover, phytochelators, obtained from plant components including vegetables and fruits, elicit iron-chelating activities; polyphenols are one such class with the ability to chelate iron with high affinity and promote health [ 31 , 32 ]. Mammalian-derived physiological iron chelators include (1) transferrin, found in blood plasma and involved in body-wide iron transport and (2) lactoferrin, enriched in neutrophils and in bodily secretions [ 32 , 33 , 34 ]. Not only do these physiological iron chelators bind iron but they also elicit anti-microbial activities to hinder the propagation of microorganisms [ 32 , 33 , 34 ].…”

“…Mammalian-derived physiological iron chelators include (1) transferrin, found in blood plasma and involved in body-wide iron transport and (2) lactoferrin, enriched in neutrophils and in bodily secretions [ 32 , 33 , 34 ]. Not only do these physiological iron chelators bind iron but they also elicit anti-microbial activities to hinder the propagation of microorganisms [ 32 , 33 , 34 ].…”

“…A subset of FDA-approved iron chelators includes DFO, DFRA, and DFP [ 26 ] and these have different means of patient administration (e.g., oral versus intravenous) with divergent efficacies and blood brain barrier accessibilities [ 32 ]. Some of the above described iron chelators have shown success in combinatorial treatment strategies with antibiotics, anti-virals, and anti-fungals.…”