Azomethine derivatives of p-ami nobenzoic acid as antioxidants and xanthine oxidase inhibitors
DOI:
https://doi.org/10.15407/dopovidi2020.06.074Keywords:
antioxidant properties, azomethines, hydroxyl radicals, inhibition, molecular docking, xanthine oxidaseAbstract
Antioxidant properties of hydroxylated azomethine derivatives of p-aminobenzoic acid and their inhibitory effect on xanthine oxidase activity have been established. Analysis of inhibitory activities of a series of synthe sized azomethine compounds towards xanthine oxidase, as well as molecular docking study indicated that carboxylate and hydroxyl groups can be involved in mechanisms of the enzyme inhibition. The azomethine derivatives are shown to exhibit the mixed type of inhibition, and inhibitory activities of some of them are in the micromolar ranges. The effect of the most active 4-(((1E)-(2-hydroxy-5-nitrophenyl)methylene)amino)benzoic acid was comparable to that of the known inhibitor allopurinol. According to molecular docking results, the carboxylate group of the azomethine inhibitor can form hydrogen bonds with the amino acid residues of Arg880, Thr1010, and Glu1261 in the active site of xanthine oxidase, while the hydroxyl group is close to the residues of Glu802 and Asn768. In addition, aryl groups of the inhibitor molecule form contacts with Phe914, Phe1009, Leu648, Phe1013, and other amino acid residues. The antioxidant activity of the azomethines is evaluated in the model system by the detection of malonic dialdehyde with the thiobarbituric acid test. The ability of some compounds to neutralize hydroxyl radicals exceeded the effect of trolox as a reference antioxidant.
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