Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

• Main Authors: Hussain, R. (Author), Imran, S. (Author), Kanwal (Author), Khan, K.M (Author), Miana, G.A (Author), Mosaddik, A. (Author), Nawaz, M. (Author), Rahim, F. (Author), Tabassum, N. (Author), Taha, M. (Author), Ullah, H. (Author), Wadood, A. (Author), Wahab, Z. (Author)
• Format: Article
• Language: English
• Published: Elsevier B.V., 2020
• Subjects: Alpha glucosidase; Aryl-oxadiazole Schiff bases; Binding energy; Diabetes mellitus; Enzymes; Glucosidase; Inhibitory activity; Molecular docking; Molecular modeling; Schiff basis; Structure-activity relationship (SAR); Structure-activity relationships; Synthesis; Synthesis (chemical); Therapeutic targets; α-glucosidase
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 18785352 (ISSN)
• ISSN: 18785352 (ISSN)
• DOI: 10.1016/j.arabjc.2020.01.005

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. © 2020