title: Synthesis and iron(III) binding properties of 3-hydroxypyrid-4-ones derived from kojic acid.
abstract: In an attempt to reduce the toxicity of the 3-hydroxypyrid-4-ones, the more hydrophilic derivatives of kojic acid were explored and compared to the standard, 1,2-dimethyl-3-hydroxypyrid-4-one, L1. The synthesis and iron(III) binding properties of these chelators are described. Neither these compounds nor the clinically effective 1,2-dimethyl-3-hydroxypyrid-4 one is able to completely remove all of the iron(III) from the Fe(III)EDTA complex in sodium acetate buffered solutions, when the 3-hydroxypyrid-4-one: Fe(III) ratio is 6:1. The ability of these compounds to enhance the urinary excretion of iron in rats indicates that the behavior of the 3-hydroxypyrid-4-ones derived from kojic acid is comparable to the analogous derivatives of maltol and ethyl maltol. The structure of the iron(III) complex of 3-hydroxy-6-hydroxymethyl-1-methylpyrid-4-one was determined by x-ray diffraction and found to be similar to the previously reported structure of the iron(III) complex of L1.
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
authors.forename: J J
authors.initials: JJ
authors.lastname: Molenda
authors.forename: M A
authors.initials: MA
authors.lastname: Basinger
authors.forename: T P
authors.initials: TP
authors.lastname: Hanusa
authors.forename: M M
authors.initials: MM
authors.lastname: Jones
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D015195:Drug Design; D004492:Edetic Acid / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds / Q000378:metabolism*; D007501:Iron / Q000652:urine; D007502:Iron Chelating Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D011728:Pyridones / Q000737:chemistry* / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005290:Ferric Compounds; D007502:Iron Chelating Agents; D011728:Pyridones; D011753:Pyrones; C020366:3-hydroxy-4-pyridone; C011890:kojic acid; D004492:Edetic Acid; D007501:Iron