期刊
FRONTIERS IN BIOSCIENCE-LANDMARK
卷 19, 期 -, 页码 862-885出版社
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/4253
关键词
Antioxidants; Antioxidant Therapy; Free Radical Toxicity; Iron; Copper; Chelators; Deferiprone; Deferoxamine; Deferasirox; Metal Ions; Targeting; Review
The design of antioxidant pharmaceuticals is a major challenge for the treatment of many clinical conditions and in aging. Free radical damage (FRD) is primarily catalysed by iron catalytic centers. Most of the natural and synthetic antioxidants are ineffective in inhibiting FRD because of the achievement of low concentrations at the affected tissues. Despite that many chelators inhibit FRD in vitro and in vivo, only Deferiprone (L1) has been shown to be effective and safe in the reversal of oxidative stress related tissue damage in iron overload and other conditions such as cardiomyopathy, acute kidney disease, Friedreich ataxia etc. Deferiprone, other chelators and their combinations could be used as main, adjuvant and alternative therapies in untreated conditions eg forms of cancer, Alzheimer's and Parkinson's diseases. Therapeutic targeting in each case requires specific chelator selection based on structure/activity correlation and consideration of other parameters eg ADMET. The ability of L1 to reach extracellular and intracellular compartments of almost all tissues including the brain is a major advantage for further development and use in many clinical conditions.
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