Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

This study evaluates the inhibition effect of new 1,4-disubstituted-1,2,3-triazoles against Xanthine Oxidase supplemented by molecular modelling. Nine compounds of 1,4-disubstituted-1,2,3-triazoles by Sharpless’s approach have been synthesized in this report. The structures of the synthesized compounds were characterized using FT-IR, ¹H and ¹³C-NMR and Mass spectroscopies Among these synthesized molecules (5-bromothiophen-2-yl)(1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl)methanone (9f) and (5-Bromothiophen-2-yl(1-(4-methoxybenzyl)-1H-1,2,3-triazole-4-yl)methanone (9h) showed better activity against Xanthine oxidase (XO) compared to allopurinol. In the light of the XO inhibition results, triazoles having of ketone moiety (9f-i) were found to be more active than triazoles of ketone-free (9a-e). These results were supported by docking models. The docking calculations of the target XO with nine available compounds showed good binding energies with favourable binding interactions. These findings were particularly evident that 9f (BE -7.29 kcal/mol) and 9h (BE -7.59 kcal/mol) are represented encouraging higher inhibition properties towards xanthine oxidase (XO), compared to allopurinol as a reference compound. Significant binding energies and interactions obtained by performing the docking studies are demonstrated, in particular, that the compounds 9f and 9h may be more potential bio compounds than the positive compounds, allopurinol, and febuxostat.

URN:NBN:sciencein.cbl.2023.v10.628