Azomethine derivatives of p-ami nobenzoic acid as antioxidants and xanthine oxidase inhibitors

TitleAzomethine derivatives of p-ami nobenzoic acid as antioxidants and xanthine oxidase inhibitors
Publication TypeJournal Article
Year of Publication2020
AuthorsKobzar, OL, Tatarchuk, AV, Kachaeva, MV, Pilyo, SG, Sukhoveev, OV, Sukhoveev, VV, Brovarets, VS, Vovk, AI
Abbreviated Key TitleDopov. Nac. akad. nauk Ukr.
DOI10.15407/dopovidi2020.06.074
Issue6
SectionChemistry
Pagination74-82
Date Published6/2020
LanguageUkrainian
Abstract

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.
Keywordsantioxidant properties, azomethines, hydroxyl radicals, inhibition, molecular docking, xanthine oxidase
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