Abstract
Iron chelating drugs are primarily and widely used in the treatment of transfusional iron overload in thalassaemia and similar conditions. Recent in vivo and clinical studies have also shown that chelators, and in particular deferiprone, can be used effectively in many conditions involving free radical damage and pathology including neurodegenerative, renal, hepatic, cardiac conditions and cancer. Many classes of phytochelators (Greek: phyto (φυτό)—plant, chele (χηλή)—claw of the crab) with differing chelating properties, including plant polyphenols resembling chelating drugs, can be developed for clinical use. The phytochelators mimosine and tropolone have been identified to be orally active and effective in animal models for the treatment of iron overload and maltol for the treatment of iron deficiency anaemia. Many critical parameters are required for the development of phytochelators for clinical use including the characterization of the therapeutic targets, ADMET, identification of the therapeutic index and risk/benefit assessment by comparison to existing therapies. Phytochelators can be developed and used as main, alternative or adjuvant therapies including combination therapies with synthetic chelators for synergistic and or complimentary therapeutic effects. The development of phytochelators is a challenging area for the introduction of new pharmaceuticals which can be used in many diseases and also in ageing. The commercial and other considerations for such development have great advantages in comparison to synthetic drugs and could also benefit millions of patients in developing countries.
Highlights
Many plant products and almost all classes of plant polyphenols found mainly in fruit and vegetables are promoted for healthy dietary reasons and considered as potent antioxidants with beneficial effects in the health of normal individuals [1]
A plant product antioxidant, including dietary antioxidants for human use, is a substance derived from plants which prevents, quenches, inhibits or decreases the toxic effects arising from free radicals, reactive oxygen species, reactive nitrogen species, as well as their toxic intermediates and other related by-products which can cause damaging effects to tissues and normal physiological functioning in humans [3,4,5,6]
The interaction of phytochelators with metallothioneins, which are able to bind a variety of metal ions by the formation of mercaptide bonds between the numerous cysteine residues present in the proteins and the metal ions are considered important in heavy metal detoxification in plants and animals [128,129]
Summary
Many plant products and almost all classes of plant polyphenols found mainly in fruit and vegetables are promoted for healthy dietary reasons and considered as potent antioxidants with beneficial effects in the health of normal individuals [1]. There are many naturally occurring low molecular weight organic molecules including phytochelators and other plant products, as well as synthetic organic molecules like medicinal drugs which possess metal ion binding groups and can form iron and other metal complexes. Plant products with metal binding properties and especially phytochelators, which can increase the size of the low molecular weight iron pool, may play a role in the urinary or faecal elimination and overall excretion of iron similar to the mode of action of the chelating drugs L1, DF, and DFRA [33]. The mode of action of phytochelators and other naturally occurring chelating molecules can have variable effects on iron metabolism and free radical toxicity, similar to those observed during the use of the chelating drugs L1, DF and DFRA [2,10]. There are prospects for the use of phytochelators in combination therapies with synthetic chelators and with other antioxidants for synergistic and or complimentary effects [9,10]
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