Orally active alpha-ketohydroxypyridine iron chelators: studies in mice.
Several N-substituted 3-hydroxypyrid-2-one and N-substituted 2-methyl-3-hydroxypyrid-4-one chelators were screened for 59Fe removal using iron-overloaded mice labeled with 59Fe. The most effectice chelators were found to be the N-methyl, N-ethyl, and N-propyl derivatives of 2-methyl-3-hydroxypyrid-4-one. When the above three chelators were administered intragastrically or intraperitoneally (200 mg/kg) to mice, they caused equivalent 59Fe excretions to intraperitoneal desferrioxamine (200 mg/kg). These results increase the prospects for the use of the alpha-ketohydroxypyridine chelators in the treatment of iron overload.
D000818:Animals; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007504:Iron Radioisotopes; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011728:Pyridones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007502:Iron Chelating Agents; D007504:Iron Radioisotopes; D011728:Pyridones; D007501:Iron; D007781:Lactoferrin