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Evaluation of novel iron chelators for therapeutic use in secondary iron overload disorders

Pyridoxal isonicotinoyl hydrazone (PIH) has been described as an orally effective Fe chelator. It is both membrane permeable and plasma soluble, and has a high affinity for Fe, making it an ideal model on which to base future chelators. Ten novel ligands have been synthesized based on these attributes. Characterization experiments were performed to determine the ligands' selectivity and binding affinity for iron, their lipophilicity as both free and Fe-ligand complexes, and their stoichiometric relationship with iron. Efficacy of the chelators has been determined through their ability to effectively mobilize non-heme 59Fe from pre-labeled cells. Intracellular levels of chelator bound 59Fe were also determined. Concentration-dependence and time-dependence mobilization experiments were performed to determine the minimal concentrations of ligands required to elicit maximal 59Fe release. Toxicity experiments with various ligand concentrations were performed in order to determine the concentration which inhibits at least half of cellular growth as compared with control. (Abstract shortened by UMI.)

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33071
Date January 2000
CreatorsMouralian, Cindy.
ContributorsPonka, Premysl (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Physiology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001838472, proquestno: MQ77063, Theses scanned by UMI/ProQuest.

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