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

Article abstract of DOI:10.1002/ddr.21782

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 (IC₅₀ 13.6?μM), Xc (IC₅₀ 13.1?μM), and Xd (IC₅₀ 12.5?μM) showed comparable inhibitory activity to allopurinol (IC₅₀ 22.1?μM). The in vitro assay result correlated well with molecular docking scores, ΔG?=??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.