Hydroxy(thio)pyrone and hydroxy(thio)pyridinone iron chelators: physico-chemical properties and anti-oxidant activity.
The O,S-donor analogues of maltol and deferiprone (DMHP), respectively, thiomaltol and DMHTP, have been investigated in solution for their iron-complexation ability, as well as their electrochemical behaviors, in the presence and absence of iron, aimed at the rationalization of their anti-oxidant activity, particularly, as hydroxyl radical scavengers and inhibitors of lipid peroxidation. The results were compared with those of the O,O-donor compounds and revealed that all the compounds are good iron chelators (pFe=14.1-20.2), but the O,S-donor ligands being somewhat weaker than the corresponding oxo-analogues. Also all the ligands appear to be able to prevent the redox cycling of iron, a relevant anti-oxidant activity, which seems to be primary due to their high capacity to form iron complexes which are not effective in promoting free radical reactions. This is a significant feature for the development of leading analogues as drug candidates with co-adjuvant roles in oxidative-stress dependent pathologies.
Centro de Química Estrutural, Instituto Superior Técnico, Universidade Técnica de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal.
Sílvia
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Chaves
Sónia
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Canário
Marta P
MP
Carrasco
Lurdes
L
Mira
M Amélia
MA
Santos
D000975:Antioxidants / Q000138:chemical synthesis*; D056831:Coordination Complexes / Q000737:chemistry*; D000077543:Deferiprone; D055664:Electrochemical Techniques; D007501:Iron / Q000737:chemistry*; D007502:Iron Chelating Agents / Q000138:chemical synthesis*; D007700:Kinetics; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry
D000975:Antioxidants; D056831:Coordination Complexes; D007502:Iron Chelating Agents; D011728:Pyridones; D011753:Pyrones; D000077543:Deferiprone; C008316:maltol; D007501:Iron