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The selection and evaluation of new chelating agents for the treatment of iron overload

CG Pitt, G Gupta, WE Estes, H Rosenkrantz, JJ Metterville, AL Crumbliss, RA Palmer, KW Nordquest, KA Hardy, DR Whitcomb, BR Byers, JE Arceneaux, CG Gaines and CV Sciortino

A large-scale systematic evaluation of potential iron chelators for the treatment of hemosiderosis was conducted. The compounds were identified and evaluated using a hypertransfused mouse screen in which deferrioxamine B was a standard. This screen was designed to measure iron depletion in the tissues as well as iron excretion. Groups of 10 previously hypertransfused BDF1 male mice received a single daily i.p. injection of either vehicle, standard, or test compound for 7 days. Iron in daily urine pools and individual spleen and liver homogenates was determined by atomic absorption. More than 70 chelators were evaluated, including natural and synthetic hydroxamic acids, phenols, catechols and tropolones known to have a high affinity for iron (III) in vitro. Ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid) was shown to be considerably more effective than deferrioxamine B (i.p.) and, in addition, was orally active. Factors determining the efficacy of this and other chelating agents are discussed.

Volume 208, Issue 1, pp. 12-18, 01/01/1979
Copyright © 1979 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics.