Novel hybrid compounds containing 1,2,3-triazole and naphthalene subunits as xanthine oxidase inhibitors

In the present study, some hybrid compounds containing 1,2,3-triazole and naphthalene subunits 16(a–g) and 17(a–f) were synthesized and characterized by ¹H, ¹³C-NMR, FT-IR, and HR-MS analyses. The in vitro inhibitor activities on the xanthine oxidase (XO) enzyme of all the target compounds were investigated and compared with allopurinol, which is one of the most common gout drugs and inhibits the XO. The activity results show that all the target compounds have potential XO inhibitor activities. The compounds showed IC₅₀ values in the range of 0.825–2.254 μM on the XO. IC₅₀ value of allopurinol on the XO was determined to be 1.475 μM. 16e and 17e compounds among them exhibited the best inhibitions compared to other compounds and allopurinol. Additionally, molecular docking studies were carried out on the 3D crystallographic structure of the XO to investigate possible interactions with the active site of the XO of all compounds. According to the docking results, all the target compounds showed that the best binding energies vary in the between − 9.71 kcal.mol⁻¹ and − 11.43 kcal.mol⁻¹. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME, ProTox-II, and Osiris Property Explorer websites and it has been predicted that the target compounds have low toxicity profiles. Consequently, the compounds can be considered new promising inhibitors for the XO.