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

被引：137

作者：

Chaston, TB ^{[1
]}

Richardson, DR ^{[1
]}

机构：

[1] Childrens Canc Inst Australia Med Res, Iron Metab & Chelat Program, Randwick, NSW 2031, Australia

来源：

AMERICAN JOURNAL OF HEMATOLOGY | 2003年 / 73卷 / 03期

关键词：

desferrioxamine; iron chelators; iron; beta-thalassemia;

D O I：

10.1002/ajh.10348

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The success of the iron (Fe) chelator desferrioxamine (DFO) in the treatment of beta-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. (C) 2003 Wiley-Liss, Inc.

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页码：200 / 210

页数：11

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