Identification of in vitro α-glucosidase and urease inhibitory effect, and in silico studies of Naproxen-derived 1,3,4-oxadiazole-based Schiff-base derivatives

•Synthesis and spectroscopic characterization of naproxen derivatives.•Isolated compounds were evaluated for in vitro α-glucosidase and urease inhibition.•A number of the compounds exhibited excellent activity, some better than the reference standards.•Binding interactions of the potent compounds with the enzymes were determined through molecular docking studies. In search of new α-glucosidase and urease inhibitors, a series of naproxen-derived 1,3,4-oxadiazole-containing ketones 6a-e and their Schiff-base derivatives 7a-o were synthesized. The isolated compounds were identified by HRMS (EI), 1H NMR and 13C NMR spectroscopic techniques. Among the series, compounds 7j, 7i, 7e, 7d and 7o were found to be significantly active against α-glucosidase with IC50 values of 6.14 ± 1.23, 9.90 ± 1.23, 25.90 ± 1.31, 38.07 ± 1.51 and 34.23 ± 1.08 µM, respectively. These values indicate a significantly higher potency compared to the standard acarbose (IC50 = 375.82 ± 1.76 µM). In the case of urease, compounds 7d, 7e, 6a, 7i and 6c showed potent inhibitory activity with IC50 values of 6.68 ± 0.97, 11.39 ± 0.10, 14.18 ± 0.38, 14.39 ± 1.05 and 18.68 ± 0.25 µM, respectively, as compared to the reference standard thiourea (IC50 = 21.37 ± 1.76 µM). The molecular docking gave an insight into the binding interactions established by the selected most active analogues with the catalytic sites of α-glucosidase and urease. The results obtained can be correlated with several key intermolecular interactions including π-cation, π-anion, π-sulphur, π-alkyl, π-π T shaped, π-π stacked, π-lone pair, hydrogen bonding and Van der Waals attraction with the active sites of α-glucosidase and urease. [Display omitted]