Development and evaluation of the improved iron chelating agents EHPG, HBED and their dimethyl esters.
The phenolic EDTA analogues ethylenediamine-N,N'-bis-(2- hydroxyphenylglycine ) ( EHPG ), N,N'-bis(2-hydroxybenzyl)-ethylenediamine diacetic acid ( HBED ), and their respective dimethyl esters ( dimethylEHPG and dimethylHBED ) were studied in hypertransfused rats. Radioiron bound to these compounds was cleared mainly by the liver and excreted in the bile. After a single 40 mg i.m. injection, the percentage of radioiron removed from 59Fe-ferritin-labelled hepatocytes and excreted in the bile was 4% in untreated controls, 24% for desferral , 42% for dimethylEHPG , 58% for EHPG , 63% for HBED , and 80% for dimethylHBED . DimethylHBED 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 iron chelating drugs.
D000284:Administration, Oral; D000818:Animals; D003676:Deferoxamine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004492:Edetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005029:Ethylenediamines / Q000627:therapeutic use; D005260:Female; D007263:Infusions, Parenteral; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007504:Iron Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D065227:Transfusion Reaction
D005029:Ethylenediamines; D007502:Iron Chelating Agents; D007504:Iron Radioisotopes; C011813:ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid); C037740:N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid; D004492:Edetic Acid; D003676:Deferoxamine