PHENOLIC ETHYLENEDIAMINE DERIVATIVES - A STUDY OF ORALLY EFFECTIVE IRON CHELATORS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 103  (3) , 337-346
Abstract
Of 35 potential Fe chelators screened for in vivo activity in rats, a group of phenolic compounds with excellent chelating properties were identified. These included N,N''-ethylene-bis(o-hydroxyphenylglycine) (EHPG), N,N''-Bis(o-hydroxybenzyl)-ethylenediamine diacetic acid (HBED), and their respective dimethyl esters (dmEHPG and dmHBED). All 4 phenolic compounds produced a marked increase in the fecal excretion of hepatocellular radioiron. This amounted to 42% of total body radioactivity with dmEHPG, 58% with EHPG, 63% with HBED and 80% with dmHBED after a single injection of 40 mg/animal. At a dose of 5 mg/animal, EHPG, HBED and dmHBED were 9, 12 and 15 times more potent, respectively, than deferoxamine. Both dimethyl esters showed significant oral activity; oral dmEHPG retained 1/3 and dmHBED retained 2/3 of the effect of the same dose given by i.m. injection. The ester dmHBED combines oral effectiveness with superior chelating ability, selective hepatocellular action and low apparent toxicity. It may represent a significant advance in the development of new Fe chelating drugs [useful in treating Fe overload in patients who require regular blood transfusions].