Iron chelators of the pyridoxal isonicotinoyl hydrazone class Part I. Ionisation characteristics of the ligands and their relevance to biological properties

Abstract

The orally effective iron chelator, pyridoxal isonicotinoyl hydrazone (PIH), and five analogues, pyridoxal benzoyl hydrazone (PBH), pyridoxal p-methoxybenzoyl hydrazone ((PpMBH), pyridoxal m-fluorobenzoyl hydrazone (PmFBH), 3-hydroxy- isonicotinaldehyde isonicotinoyl hydrazone (IIH) and salicylaldehyde isonicotinoyl hydrazone (SIH) were synthesised and characterised and their acid dissociation constants measured by glass electrode potentiometry and UV-Vis spectrophotometry. Analysis of the data showed that at physiological pH all of the ligands are predominantly (av. 80%) in the form of the neutral molecule, allowing passage through cell membranes and access to intracellular iron pools. The results are discussed in the context of the development of an orally effective iron chelator for clinical use. © 1990.