Our laboratory identified pyridoxal isonicotinoyl hydrazone (PIH) as an orally effective Fe chelator (BBA 586:278 1979). More recent in vitro and in vivo studies with PIH analogs have demonstrated that halogenated pyridoxal benzoyl hydrazones are more effective iron chelators than PIH. In this study, 33 analogues were synthesized and assessed. The compounds were derived from 3 parent aldehydes: pyridoxal (100 series), salicylaldehyde (200 series) and 2-hydroxy-1-naphthylaldehyde (300 series) in combination with the ortho-, meta -, and para-isomers of halogenated benzhydrazides: chloro (08), fluoro (09), bromo (10), and iodo (10.1). Fe chelators were evaluated on the basis of their ability to mobilize Fe59 in vitro from (i) murine reticulocytes with a high level of non-heme Fe59 and (ii) Fe59 loaded K562 cells. Following incubation of Fe59 loaded cells in the presence of chelators, we also determined the intracellular level of chelator-bound Fe59 that remains in solution following ethanol precipitation of cellular proteins. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.29871 |
| Date | January 1999 |
| Creators | Arduini, Emmanuele. |
| Contributors | Ponka, Prem (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001681915, proquestno: MQ55036, Theses scanned by UMI/ProQuest. |
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