Advances in iron chelation: an update

Abstract

A number of iron chelators are used as approved therapeutic agents in the treatment of thalassemia major, asthma, fungal infections and cancer. However, as our knowledge about the biochemistry of iron and its role in etiologies of seemingly unrelated diseases increases, new applications of the approved iron chelators, as well as the development of new iron chelators, present challenging opportunities in the areas of drug discovery and development.

Ferritin iron uptake and release in the presence of metals and metalloproteins: Chemical implications in the brain

“…Eight hydrophilic channels of [4][5] Å in diameter and with C3 symmetry (Fig. 1) allow the transfer of water, metal cations and hydrophilic molecules of the appropriate size from the external solution to the cavity or vice versa.…”

“…Among these, the most common one is the Fenton reaction, in which hydroxyl radicals OH• are produced by the reaction of iron(II) and hydrogen peroxide. ROS are extremely powerful oxidizing agents capable of causing irreversible cell damage, organ failure and eventually death [4]. Furthermore, free iron is a key nutrient for pathogenic microorganisms, which require iron to survive and replicate.…”

Antibacterial Activities of Iron Chelators against Common Nosocomial Pathogens

“…Numerous studies have assessed the potential viability of iron chelators as therapeutic agents against various microbes, but with only mixed success (4, 6-8, 10-17, 20, 24, 25, 27). Nevertheless, as novel iron chelators are developed for treatment applications such as neurodegenerative diseases (3,9,19) or ␤-thalassemia (3,9), an evaluation of their antimicrobial activities should be tested, because their efficacies against bacteria may be superior to chelators previously tested. In the case of multidrug-resistant (MDR) bacteria, where entire classes of antibiotics are no longer treatment options (1,21), iron chelators that have already undergone toxicity and preclinical testing in animals might provide an alternative treatment approach.…”

“…Deferiprone has also been shown to have antibacterial properties against certain bacterial species in vitro (4,10). Deferiprone (ApoL1) and Apo6619 were provided by ApoPharma, Inc., and VAR10100 (VK28 dihydrochloride) was provided by Varinel, Inc. Because of their iron chelation properties, both Apo6619 and VK28 (and their derivatives) are currently being studied for treatment applications (9,19,22,28). Deferoxamine mesylate salt (DFO) and 2,2=-bipyridyl (DIP) were purchased from Sigma-Aldrich Inc. and were evaluated for comparison purposes.…”

Iron Chelating Agents for Iron Overload Diseases

“…Chelation therapy was introduced in clinical practice in the seventies of last century to defend thalassemic patients from the toxic effects of iron overload. Among the numerous tasks of iron chelating agents, deeply discussed in several reviews, [3][4][5][6][7][8] the main ones consist in creating a favorable equilibrium between transfusional iron assumed by patients and that excreted in a chelated form, in protecting against the circulating non transferrin bound iron which via Fenton reaction easily leads to ROS production, and in scavenging iron stores from organs and tissues in which exert their toxic action. The quantification of iron stores in tissues can be accomplished by iron determination in liver biopsies, 9,10 or by magnetic resonance imaging 11 or by superconducting quantum interference device magnetic susceptibility.…”