Disease relevance of AIDS081859

• The present study analyzes the iron mobilization, the cytoprotective, and the antiproliferative effects of the lipophilic hydroxypyridinone CP411, in comparison with the hydrophilic chelator CP20 or deferiprone used in the treatment of iron overload [1].
• The iron chelating hydroxypyridinone, CP94, has been administered prophylactically to iron overloaded gerbils in a dosing regime which favors the formation of bidentate chelated iron, to examine the possibility of additional toxicity being caused to the liver and heart by the bidentate chelated iron complex [2].

High impact information on AIDS081859

• A series of bidentate hydroxypyridinone iron chelators that have therapeutic potential as oral iron chelators, have been studied systematically to determine which properties are the most critical for the mobilization of hepatocyte iron [3].
• The environment of the lipoxygenase iron binding site explored with novel hydroxypyridinone iron chelators [4].
• The different physiochemical characteristics of relatively hydrophobic low molecular weight bidentate hydroxypyridinone chelators and the higher molecular weight hexadentate ferrioxamine have been exploited to elucidate these interactions further [5].
• Removal of iron is not the only mechanism by which hydroxypyridinones can inhibit lipoxygenase in intact cells, however, as a lipophilic non-iron-binding hydroxypyridinone, which shows no inhibition of the soybean lipoxygenase activity, partially inhibits 5-lipoxygenase in intact neutrophils without inhibiting neutrophil phospholipase A2 [4].
• Electron paramagnetic resonance studies show the removal of the iron center signal (g = 6) is concomitant with formation of Fe(III)-chelator complexes, identical in spectral shape and g value to 3:1 hydroxypyridinone Fe(III) complexes [4].

Biological context of AIDS081859

• Deferoxamine augments growth and pathogenicity of Rhizopus, while hydroxypyridinone chelators have no effect [6].
• Iron mobilization, cytoprotection, and inhibition of cell proliferation in normal and transformed rat hepatocyte cultures by the hydroxypyridinone CP411, compared to CP20: a biological and physicochemical study [1].
• In order to define a predictive animal model for the effects of hydroxypyridinone (HPO) iron chelators in humans, we have compared the 28 d oral efficacy and toxicology of the HPO, 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rats and guinea-pigs and related the results to the contrasting metabolism of this compound in the two species [7].

Anatomical context of AIDS081859

• The chelation of nonheme iron within sickle erythrocytes by the hydroxypyridinone chelator CP094 [8].
• Potentiation of iron accumulation in cardiac myocytes during the treatment of iron overload in gerbils with the hydroxypyridinone iron chelator CP94 [2].

Associations of AIDS081859 with other chemical compounds

• The 2-hydroxypyridine-N-oxide derivatives, 2-hydroxypyridine-N-oxide, 2,4-dihydroxypyridine-N-oxide, 2-hydroxy-4-methoxypyridine-N-oxide and 2-hydroxy-4-(2'-methoxyethoxy)pyridine-N-oxide have been shown to remove iron from human transferrin and horse spleen ferritin at pH 7.4 at levels higher than those caused by desferrioxamine [9].

Gene context of AIDS081859

• Deferiprone (L1; CP20) is an orally absorbed bidentate hydroxypyridinone iron chelator that can induce urinary iron excretion, promote negative iron balance and reduce hepatic iron levels in some transfusion-dependent patients, particularly in those who are markedly iron overloaded and have not received regular deferoxamine therapy [10].
• Effect of orally active hydroxypyridinone iron chelators on human lymphocyte function [11].
• These analogues contain one, two, or three bidentate 2,3-dihydroxyterephthalamide (TAM) units in place of the 3,2-hydroxypyridinone (HOPO) units on the parent hexadentate ligand [12].

Analytical, diagnostic and therapeutic context of AIDS081859

• Enhancement of 5-aminolaevulinic acid-induced photodynamic therapy in normal rat colon using hydroxypyridinone iron-chelating agents [13].

References