2-Hydroxypyridine-N-oxides: effective new chelators in iron mobilisation.
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. Their reactions with transferrin were mainly biphasic and took 2-5 h to reach completion but iron mobilisation from ferritin was slower and their reactions continued after 40 h of incubation. The intraperitoneal and intragastric administration of 2,4-dihydroxypyridine-N-oxide to two iron-loaded 59Fe-labelled mice caused an increase in 59Fe excretion which is comparable to that caused by desferrioxamine intraperitoneally. These results increase the prospects for the use of these chelators as probes for studying iron metabolism and in the treatment of iron overload and other diseases of iron imbalance.
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D003676:Deferoxamine / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism*; D006736:Horses; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D011725:Pyridines / Q000494:pharmacology*; D013154:Spleen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000378:metabolism*
D002614:Chelating Agents; D003497:Cyclic N-Oxides; D011725:Pyridines; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D003676:Deferoxamine