Synthesis and docking studies of pyrazole-benzamide-benzothiazole conjugates as xanthine oxidase inhibitor candidates

A series of benzothiazole bearing pyrazole derivatives (6a-j) were synthesized via mechanochemical synthesis through hand grinding using pestle and mortar, and their xanthine oxidase inhibition efficiency and antioxidant properties were evaluated. The 1H NMR, 13C NMR, FT-IR, and mass spectroscopy techniques were employed for the characterization of the synthesized molecules. Initially, the xanthine oxidase (XO) enzyme inhibitory activity for all the compounds (6a-j) was performed using standard reference. Further, for the potent compound (6h) with methyl sulphonyl substitution in the benzothiazole ring the kinetic analysis of XO was carried out. Later, anti-oxidant assays like DPPH, ABTS, and superoxide radical scavenging assays for title compounds were conducted. Also in these assays, the compound (6h) was found to exhibit good antioxidant activity, and the inhibitory constant of XO was found to be 1.78 µg. Furthermore, the docking and dynamic studies were carried out, and the compound (6h) was found to show the lowest binding energy. Also, the analysis of RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds of the compound (6h) was conducted and the binding free energy of the compound (6h) was calculated.