Design, synthesis, in vitro evaluation, and docking studies on ibuprofen derived 1,3,4-oxadiazole derivatives as dual α-glucosidase and urease inhibitors

Present study aimed at the discovery of new non-sugar α -glucosidase inhibitors includes synthesis of a series of 1,3,4-oxadiazole based Schiff base derivatives of ibuprofen. Initially oxadiazoles from ibuprofen were synthesized by treating ibuprofen hydrazide with carbon disulfide. Oxadiazoles upon treatment with different substituted phenacyl bromides give acylated 1,3,4-oxadizole derivatives 6(a–e) which further react with amines to give 1,3,4-oxadiazole based Schiff base derivatives of ibuprofen 7(a–o) . The synthesized ibuprofen derivatives were characterized by 1 H NMR, 13 C NMR and HRMS (EI). These derivatives were evaluated in vitro for their α -glucosidase and urease inhibitory activity. In case of α -glucosidase enzyme, all the synthesized derivatives showed potent inhibition in comparison to standard acarbose and the most potent amongst these are the compounds 7o and 7b having IC 50 value 16.01 ± 1.27 µM and 39.06 ± 0.27 µM, respectively. In case of urease enzyme, the synthesized derivatives showed varying degree of inhibitory potential, however, potent inhibition was shown by 6d (IC 50 = 9.36 ± 1.02 µM), 6c (IC 50 = 17.65 ± 1.03 µM), 7o (IC 50 = 18.29 ± 1.26 µM), 6a (IC 50 = 19.52 ± 1.25 µM) and 7j (IC 50 = 19.63 ± 1.08 µM). The molecular docking was performed in order to check binding interactions between the synthesized derivatives and the enzymes.