Using standard in vitro drug susceptibility methods, we assessed the antimalarial activity of 3 orally administered iron chelators (hydroxypyridinones) alone and in combination with conventional antimalarials drugs (quinine, mefloquine, artesunate, tetracycline, atovaquone) against a chloroquine-resistant Plasmodium falciparum isolate. When tested alone, all iron chelators and antimalarial comp...

A series of ortho-hydroxypyridine-4-ones were prepared in high yields and evaluated for antioxidant and iron chelating activities. N(1)-H hydroxypyridinones Va, Vb, and Ve were the best radical scavengers in DPPH free radical scavenging assay. Compound Vb was proved to be the most potent compound in hydrogen peroxide scavenging assay. All of the synthesized compounds had very close chelating ab...

hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (dfo). in the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (mhpo), was studied in iron overloaded rats and compared with those of dfo. for iron overloading, rats received i.p. inject...

Tripodal hexadentate hydroxypyridin-4-ones are increasingly utilised as iron(III) and gallium(III) ligands, their attachment to proteins being particularly useful for positron emission tomography (PET). A widely studied tripodal ligand NTA(BuHP)3, which is reported to form 1:1 iron(III) and gallium(III) complexes in aqueous, media forms 2:2 complexes under physiological conditions. This importa...

Synovial iron deposition associated with rheumatoid disease may result in the production of highly reactive oxygen free radicals, leading to tissue damage. This chain of events can be interrupted by iron chelation. Families of strong iron (III) chelators have been tested for their iron scavenging properties in vitro and their effects assessed in vivo using a rat model of inflammation. All the c...

transfusion-dependent patients such as those suffering from β-thalassaemia develop a fatal secondary haemosiderosis and consequently a selective iron chelator must be used to relieve such iron overload. 3- hydroxypyridin-4-ones are selective for iron(iii) under most biological conditions, but unlike desferrioxamine, are efficiently absorbed when administered orally. in this study, the synthesis...

iron overload is a serious clinical condition which can be largely prevented by the use of iron-specific chelating agents. in this study, the synthesis and determination of partition coefficients (kpart) of a range of n-alkyl hydroxypyridinones, as orally active iron chelators, are described. synthesis of n-aryl hydroxypyridinones was achieved via a single step synthetic pathway. in this method...

A number of iron-chelating agents are currently being considered as orally active alternatives to desferrioxamine (DFO), the therapeutic agent for the treatment of body iron overload that is available at present. These include bidentate hydroxypyridinones (HPO), tridentate desferrithiocin (DFT) analogues and hexadentate aminocarboxylate (HBED) chelators. All chelating agents have the potential ...

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to th...