| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1311081 | Inorganica Chimica Acta | 2011 | 8 Pages |
4-Hydroxy-6-methyl-3-pyridinecarboxylic acid (DQ6) and the new compound 2,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ726) were evaluated for possible application for iron (Fe) and aluminium (Al) chelation therapy. Metal/ligand solution chemistry, cytotoxicity, octanol/water partitioning (Do/w), and chelation efficiency were studied. The solution chemistry of the two ligands with Fe(III) and Al(III) was investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations, UV–Vis spectrophotometry, and 1H NMR spectroscopy. DQ6 exhibited a high coordination efficiency towards Al(III). Fe(III)/DQ6, Al(III)/DQ726, and Fe(III)/DQ726 complexes were less stable. These results were confirmed by chelation efficiency measurements performed in an octanol/aqueous solution. Accordingly, the effects of the substitution at various ring positions of 4-hydroxy-3-pyridinecarboxylic acid were rationalised. Partitioning experiments at pH 7.4 showed both DQ6 and DQ726, and their Fe(III) and Al(III) complexes, to be hydrophilic. The toxicity of DQ6 and of DQ726 was investigated with human cancer cell lines and normal human primary cells: no cytotoxic effects were observed up to 0.1 mM, following a 3 days exposure. According to our results, DQ6 has the favourable properties to be a chelating agent for Al.
Graphical abstract4-Hydroxy-6-methyl-3-pyridinecarboxylic acid (DQ6) and 2,6-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ726) were evaluated for possible application for Fe and Al chelation therapy. Metal/ligand solution chemistry, cytotoxicity, octanol/water partitioning, and chelation efficiency were studied. DQ6 has the favourable properties to be a chelating agent for Al.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► New compounds DQ6 and DQ716 evaluated as chelating agents for Fe and Al. ► They form strong complexes with Fe(III) and Al(III) in aqueous solution. ► They are hydrophilic, have good chelation efficiency in vitro, are not cytotoxic. ► DQ6 can be proposed as chelating agent for Al.
