The development of new iron-chelating drugs. II

RW Grady, JH Graziano, GP White, A Jacobs and A Cerami

For the past several years, we have searched for an orally effective iron-chelating drug and report here on several compounds which warrant further investigations based on their ability to promote iron excretion in the hypertransfused rat. Administrered orally, 2,3- dihydroxybenzyolglycine induced both urinary and fecal iron excretion, suggesting that a conjugate of 2,3-dihydroxybenzoic acid may be more efficacious than the parent compound. Tropolone, although rather toxic, stimulated fecal excretion of iron when given p.o. at low doses. Evaluation of less toxic derivatives of tropolone appears to be justifiable. L-Histidine may also be of use in chelatin therapy. Fecal iron excretion is significantly increased in response to oral doses of this essential amino acid. Lastly, cholylhydroxamic acid proved to be the most efficacious oral agent examined thus far. A marked increase in fecal iron excretion results from its administration.

Volume 205, Issue 3, pp. 757-765, 06/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics