In silico design and synthesis of N‐arylalkanyl 2‐naphthamides as a new class of non‐purine xanthine oxidase inhibitors

Abstract A series of N ‐arylalkanyl 2‐naphthamides ( Xa ~ e ), which were predicted from virtual molecular docking on a built xanthine oxidase template as potential inhibitors, were synthesized. Their inhibitory activity against xanthine oxidase was assayed. Among these prepared, compounds Xb (IC 50 13.6 μM), Xc (IC 50 13.1 μM), and Xd (IC 50 12.5 μM) showed comparable inhibitory activity to allopurinol (IC 50 22.1 μM). The in vitro assay result correlated well with molecular docking scores, Δ G = −16.99, −17.66, and −17.13 Kcal/mol, respectively. On the potassium oxonate‐induced hyperuricemic mice model, oral administration of Xc ‐ Ac (40 mg/ Kg), the per‐ O ‐acetylated Xc , could reduce the blood uric acid level by 60% in comparison to the normal control group and is statistically significant ( p < .01) while compared with the hyperuricemic mice group.