Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity |
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| Authors: | D R Richardson Paul V Bernhardt |
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| Institution: | (1) Department of Medicine, University of Queensland, Clinical Sciences Building Floor C, Royal Brisbane Hospital, Herston Brisbane, Queensland 4029, Australia e-mail: D.Richardson@medicine.herston.uq.edu.au Tel.: +61-7-33655121, Fax: +61-7-33655462, AU;(2) Department of Chemistry, University of Queensland, Brisbane Queensland 4072, Australia, AU |
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| Abstract: | Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone
chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined
the structure and properties of NIH and its FeIII complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination
to FeIII in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of Fe(NIH–H)2]+ shows that the trivalent oxidation state is dominant over a wide potential range and that the FeII analogue is not a stable form of this complex. The fact that Fe(NIH–H)2]+ cannot cycle between the FeII and FeIII states suggests that the production of toxic free-radical species, e.g. OH
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or O2
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–, is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that
the addition of FeIII to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its FeIII complex are discussed in the context of understanding its anti-tumour activity.
Received: 12 November 1998 / Accepted: 9 February 1999 |
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| Keywords: | Crystal structure Iron chelators Anti-tumour agent |
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