Development of novel aroylhydrazone ligands for iron chelation therapy: 2-Pyridylcarboxaldehyde isonicotinoyl hydrazone analogs☆,☆☆,★
Section snippets
Synthesis of iron chelators and their preparation for screening in culture
The seven PCIH analogs were synthesized by Schiff base condensation between 2-pyridinecarboxaldehyde and the respective acid hydrazides with standard procedures.28 The chelators were characterized by a combination of elemental analysis, infrared spectroscopy, 1H-NMR spectroscopy, and x-ray crystallography. The chemical characterization of these chelators will be reported in a subsequent publication. Both PIH and the PIH analog 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) were
Effect of the chelators on iron release from prelabeled cells and iron uptake from transferrin
The ability of the seven PCIH analogs to increase 59Fe release from SK-N-MC cells was compared with that of “standard” chelators (DFO, PIH, and 311) whose activity has been documented previously in this cell line.17, 30 The efflux of 59Fe from SK-N-MC cells was examined after a 3-hour labeling period with 59Fe-Tf (0.75 μmol/L) followed by a 3-hour reincubation in the presence and absence of DFO (100 μmol/L) or the remainder of the ligands at 50 μmol/L (Fig 2, A ).
Discussion
In this study we have synthesized and screened seven novel aroylhydrazone ligands based on PCIH. Three of these chelators, namely PCBH, PCBBH, and PCTH, showed Fe chelation activity that was greater than DFO and comparable to that of PIH and 311. In addition, the antiproliferative activity of these chelators was far less than that found for analog 311, an aroylhydrazone ligand previously shown to possess high cytotoxic activity.17, 18 These properties suggest that these three PCIH analogs would
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Cited by (0)
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Supported by the Friedreich's Ataxia Support Group of Queensland in the form of a PhD Scholarship (E.B.) and by a grant from the National Health and Medical Research Council of Australia (D.R.R.). D.R.R was supported by a Research Fellowship and Senior Research Fellowship from the Department of Medicine, University of Queensland.
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Reprint requests: Des R. Richardson, PhD, Department of Medicine, Clinical Sciences Building Floor C, Royal Brisbane Hospital, Brisbane, Queensland, Australia 4029.
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0022-2143/99 $8.00 + 0 5/1/100866