M. A. Santos
Jun 3, 2002
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Influential Citations
70
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Journal
Coordination Chemistry Reviews
Abstract
Abstract Hydroxypyridinones are a class of dioxo ligands under active development, as efficient Al (and Fe) chelators for potential medical uses. A wide range of those compounds has been designed aimed at improving their physico-chemical and pharmacokinetic properties. In this paper, we make a review on the literature results related to the design, chemistry, metal binding interaction, lipo-hydrophilic character and some biological assays of bidentate and hexadentate hydroxypyridinones. Among the different types of hydroxypyridinones, the 3-hydroxy-4-pyridinones deserved special attention because they are good orally active aluminium-chelators, and they seem to be the main candidates for replacement of desferrioxamine. The interaction of the bidentate hydroxypyridinones with Al as well as the in vivo studies have been more systematically reported than those of the hexadentate derivatives. The development of the hexadentate hydroxypyridinones is quite recent but, at physiological conditions, they have higher affinity for these M3+ ions than the bidentate derivatives. Despite only studies on hexadentate hydroxypyridinone–iron interactions are known and described herein, special attention was deserved to these results because of the in vivo/vitro similarity between the physico-chemical properties of these ions. The high Al affinity and favourable lipo-hydrophilic balance of the hydroxypyridinones suggest that their use as Al scavengers should be highly considered in future prospects.