Effect of pyridoxal isonicotinoyl hydrazone and other hydrazones on iron release from macrophages, reticulocytes and hepatocytes.
A model consisting of 59Fe-labelled macrophages was developed for screening potential iron-chelating drugs. Mouse peritoneal macrophages, induced by previous intraperitoneal injections of 3% thioglycollate, were labelled in vitro by their exposure to immune complexes of 59Fe-transferrin-antitransferrin antibody. Optimal conditions for macrophage labelling and subsequent 59Fe release were established. Sixty-two aromatic hydrazones, the majority of which had iron binding structures similar to pyridoxal isonicotinoyl hydrazone, were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde, 2-hydroxy-1-naphthylaldehyde and 2-furaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring. These compounds were examined for their potential to stimulate 59Fe release from 59Fe-labelled macrophages and also from reticulocytes and hepatocytes loaded with non-heme 59Fe. The majority of hydrazones derived from pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde seemed to be equally effective in both the macrophage and reticulocyte testing systems. However, the pyridoxal hydrazones were much more active in hepatocytes than the other groups of hydrazones. Several compounds proved to be very potent in mobilizing 59Fe. These included hydrazones derived from 2-hydroxy-1-naphthylaldehyde and benzoic acid hydrazide, p-hydroxybenzoic acid hydrazide, 2-thiophenecarboxylic acid hydrazide, and also pyridoxal benzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-thiophenecarboxyl hydrazone.
Ponka
P
P
Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Canada.
Richardson
D
D
Baker
E
E
Schulman
H M
HM
Edward
J T
JT
D000818:Animals; D006835:Hydrazones / Q000494:pharmacology; D007501:Iron / Q000493:pharmacokinetics*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism*
D006835:Hydrazones; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D007501:Iron; D007538:Isoniazid