Iron chelators for the treatment of iron overload disease: Relationship between structure, redox activity, and toxicity

The success of the iron (Fe) chelator desferrioxamine (DFO) in the treatment of β‐thalassemia is limited by its lack of bioavailability. The design and characterization of synthetic alternatives to DFO has attracted much scientific interest and has led to the discovery of orally active chelators tha...

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Bibliographic Details
Published inAmerican journal of hematology Vol. 73; no. 3; pp. 200 - 210
Main Authors Chaston, Timothy B., Richardson, Des R.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2003
Wiley-Liss
Subjects
Anemias. Hemoglobinopathies
Biological and medical sciences
Deferoxamine - pharmacology
desferrioxamine
Diseases of red blood cells
General and cellular metabolism. Vitamins
Hematologic and hematopoietic diseases
Humans
iron
Iron - deficiency
Iron - metabolism
Iron Chelating Agents - therapeutic use
iron chelators
Iron Overload - classification
Iron Overload - drug therapy
Medical sciences
Pharmacology. Drug treatments
β‐thalassemia
Human
Hemoglobinopathy
Cell oxidation
Toxicity
Hemopathy
Deferiprone
Iron
Review
Biological activity
Genetic disease
Deferoxamine
Chemotherapy
Hemolytic anemia
Treatment
Structure activity relation
Overload
β-Thalassemia
Animal
Chelating agent
Mechanism of action
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Summary:The success of the iron (Fe) chelator desferrioxamine (DFO) in the treatment of β‐thalassemia is limited by its lack of bioavailability. The design and characterization of synthetic alternatives to DFO has attracted much scientific interest and has led to the discovery of orally active chelators that can remove pathological Fe deposits. However, chelators that access intracellular Fe pools can be toxic by either inhibiting Fe‐containing enzymes or promoting Fe‐mediated free radical damage. Interestingly, toxicity does not necessarily correlate with Fe‐binding affinity or with chelation efficacy, suggesting that other factors may promote the cytopathic effects of chelators. In this review, we discuss the interactions of chelators and their Fe complexes with biomolecules that can lead to toxicity and tissue damage. Am. J. Hematol. 73:200–210, 2003. © 2003 Wiley‐Liss, Inc.
ISSN:0361-8609
1096-8652
DOI:10.1002/ajh.10348