Antioxidant action of pyridine compounds was analyzed in relation to the metal coordination. Iron-mediated lipid peroxidation, determined as the formation of thiobarbituric acid-reactive substances, was inhibited by dipicolinic acid (pyridine 2,6-dicarboxylic acid), but not by other pyridine dicarboxylates including quinolinic acid, lutidinic acid, cinchomeronic acid, isocinchomeronic acid. Dipicolinic acid further protected some enzymes against copper-mediated oxidative inactivation. Copper-catalyzed formation of hydroxyl radical causing oxidative inactivation of AMP deaminase was inhibited by dipicolinic acid under the in situ conditions of yeast cells. Dipicolinic acid further attenuated the inhibition by copper ion of glutathione reductase. However, other pyridine dicarboxylates did not show any protective effect. Dipicolinic acid enhanced the autooxidation of Fe2+ ion, whereas other pyridine carboxylates rather inhibited the autooxidation of ferrous ion. Ascorbate-catalyzed production of Cu+ ion, a potent prooxidant, from Cu2+ ion was completely inhibited by dipicolinic acid.
Antioxidant effect of dipicolinic acid can be explained by enhancement of the oxidation of ferrous ion, and by the inhibition of the formation of cuprous ion as a prooxidant: this may be due to the electron-deficient nature of pyridine ring with dicarboxylic acid at ortho position followed by binding of iron and copper ions.
