Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture

HepatologyVolume 15, Issue 3 p. 492-501 Original ArticleFree Access Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture Dr. Erica Baker, Corresponding Author Dr. Erica Baker Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSenior Research Fellow, National Health and Medical Research Council of Australia, Department of Physiology, University of Western Australia, Perth, Western Australia 6009, Australia===Search for more papers by this authorDes Richardson, Des Richardson Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSearch for more papers by this authorSharon Gross, Sharon Gross Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSearch for more papers by this authorPrem Ponka, Prem Ponka Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital and Department of Physiology, McGill University, Montreal, Quebec, Canada H3T 1E2Search for more papers by this author Dr. Erica Baker, Corresponding Author Dr. Erica Baker Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSenior Research Fellow, National Health and Medical Research Council of Australia, Department of Physiology, University of Western Australia, Perth, Western Australia 6009, Australia===Search for more papers by this authorDes Richardson, Des Richardson Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSearch for more papers by this authorSharon Gross, Sharon Gross Department of Physiology, University of Western Australia, Perth, Western Australia 6009, AustraliaSearch for more papers by this authorPrem Ponka, Prem Ponka Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital and Department of Physiology, McGill University, Montreal, Quebec, Canada H3T 1E2Search for more papers by this author First published: March 1992 https://doi.org/10.1002/hep.1840150323Citations: 111AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract A range of new analogues of the promising iron chelator pyridoxal isonicotinoyl hydrazone was prepared and assessed for activity in reducing hepatocyte iron, mechanism of action and potential in iron-chelation therapy. A total of 45 compounds were synthesized by condensation of aromatic aldehydes (pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde) with various acid hydrazides prepared by systematic substitutions on the benzene ring or by the replacement of the ring with an acetyl, pyridyl, furoyl or thiophene moiety. The effects of these compounds on 59Fe uptake and intracellular distribution in hepatocytes in culture and on 59Fe mobilization from prelabeled hepatocytes were assessed. Toxicity, lipophilicity and the ability to chelate plasma transferrin-bound 59Fe were also evaluated. Several compounds were much more active than pyridoxal isonicotinoyl hydrazone and may have clinical potential. These included pyridoxal benzoyl hydrazone, pyridoxal p-methoxybenzoyl hydrazone, pyridoxal m-fluorobenzoyl hydrazone and pyridoxal 2-pyridyl hydrazone. All were more effective at reducing iron uptake than mobilizing hepatocyte iron; they also may act primarily on the transit iron pool rather than on storage iron. Other compounds (e.g., salicylaldehyde p-t-butyl-benzoyl hydrazone) redistributed ferritin-59Fe to different intracellular sites but had little net effect on hepatocyte iron levels. (Hepatology 1992;15:492–501). References 1 Modell B, Berdoukas V. The clinical approach to thalassemia. New York: Grune & Stratton, Inc., 1984. 2 AE Martell, WF Anderson, DG Badman, eds. Development of iron chelators for clinical use. New York: Elsevier-North Holland, 1981. 3 Peter H. Industrial aspects of iron chelators: pharmaceutical applications. In G Spik, J Montreuil, RR Crichton, J Mazurier, eds. Proteins of iron storage and transport. New York: Elsevier Science Publishers, 1985: 293– 303. 4 Martell AE, Motekaitis RJ, Murase I, Sala LF, Stoldt R, Ng CY. Development of iron chelators for Cooley's anemia. 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