Evaluation of potential aluminum chelators in vitro by aluminum solubilization ability, aluminum mobilization from transferrin and the octanol/aqueous distribution of the chelators and their complexes with aluminum.
Representative amino acids, carboxylic acids, a ketone, hydroxamic acids, 3-hydroxypyridinones and a linear catecholcarboxyamide were tested in vitro to estimate their aluminum (Al) chelation potential. Their ability to solubilize Al from insoluble Al borate in a previously described octanol/aqueous (o/a) system was tested. Salicylhydroxamic acid, rhodotorulic acid, the 3-hydroxypyridin-4-ones and a sulfonated linear polycatecholcarboxamide significantly increased solubilized Al, suggesting Al chelation potential. Some of the above compounds and some compounds previously shown to solubilize Al in the o/a system were tested for their ability to mobilize Al from the Al plasma binding protein transferrin. Chelators solubilizing Al in the o/a system were comparably effective in mobilizing Al from transferrin, supporting the utility of the o/a system as a screening method. The o/a distribution coefficient of each chelator was determined, when possible, to assess its hydrophilicity. When compared with the suggested desirable hydrophilicity of effective chelators, the o/a distribution coefficient of many of the 3-hydroxypyridin-4-ones and a sulfonated linear polycatecholcarboxamide suggest that they might be able to chelate intracellular Al. The o/a distribution coefficient of each Al-chelator complex was determined, when possible, to predict the likelihood of redistribution within or excretion from the intact animal of this complex. Complexation of chelators with Al usually increased chelator hydrophilicity. The results suggest several compounds that warrant further investigation as potential alternatives to desferrioxamine in the treatment of Al accumulation and toxicity.
Yokel
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RA
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Datta
A K
AK
Jackson
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EG
D020003:1-Octanol; D000535:Aluminum / Q000737:chemistry / Q000378:metabolism*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D000442:Octanols / Q000032:analysis; D012995:Solubility; D014168:Transferrin / Q000378:metabolism*
D002614:Chelating Agents; D000442:Octanols; D014168:Transferrin; D000535:Aluminum; D020003:1-Octanol