Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies
Hayat Ullah, Fazal Rahim, Muhammad Taha, Raffaqat Hussain, Nida Tabassum, Abdul Wadood, Mohsan Nawaz, Ashik Mosaddik, Syahrul Imran, Zainul Wahab, Ghulam Abbas Miana, Kanwal, Khalid Mohammed Khan
Abstract
α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data.