Oral iron chelators – development and application

Iron chelation therapy is the only therapeutic approach that leads to enhanced iron excretion in β-thalassaemia major and other transfusion-dependent patients. Although desferrioxamine has been used in such treatment over the last three decades, it is not an ideal drug due to its poor oral availability. Consequently extensive research effort has been directed towards the identification of non-toxic, orally active iron chelators. An ideal candidate must possess a range of critical physicochemical and biological properties, such as high selectivity and affinity for iron(III), tightly controlled distribution and metabolic profiles and low toxicity. Unfortunately, hexadentate ligands are generally associated with poor oral bioavailability, whereas many tridentate and bidentate molecules are orally active. The tridentate triazoles have been investigated for clinical potential; they are readily absorbed from the gastrointestinal tract and promote iron excretion with high efficacy. In similar fashion, several bidentate hydroxypyridinones have been demonstrated to possess potential as oral chelating agents.