DEVELOPMENT OF NEW IRON-CHELATING DRUGS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 196  (2) , 478-485
Abstract
2,3-Dihydroxybenzoic acid was identified as a potentially useful Fe-chelating drug. Accordingly, a series of derivatives of hydroxylated benzoic acids were evaluated for their ability to induce Fe excretion in the Fe-overloaded rat. A number of hydroxamic acids and some other naturally occurring Fe-chelating agents were examined. Of the 26 benzoic acid derivatives studied, none appeared more effective than 2,3-dihydroxybenzoic acid. Rhodotorulic acid, a hydroxamic acid produced by and isolated from cultures of Rhodotorula pilimanae, was the most effective of all compounds studied in inducing Fe excretion. When administered parenterally, rhodotorulic acid induced Fe excretion by both the urinary and the fecal routes and was more than twice as potent (on a weight basis) as desferrioxamine. Two ferrous chelators, .alpha.,.alpha.-dipyridyl and 1,10-phenanthroline, induced a moderate amount of Fe excretion, suggesting that a pool of ferrous Fe may be available for chelation. Every compound for which there was no reported median lethal dose (LD50) was screened for toxicity in mice.