Synthesis of Benzofuran–based Schiff bases as anti-diabetic compounds and their molecular docking studies

• Published in: Journal of Molecular Structure
• Main Author: Adalat B.; Rahim F.; Taha M.; Hayat S.; Iqbal N.; Ali Z.; Shah S.A.A.; Wadood A.; Rehman A.U.; Khan K.M.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2022
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85130594185&doi=10.1016%2fj.molstruc.2022.133287&partnerID=40&md5=6107d068b81c577eeee2e01f8c6c8803

Inhibition of α-glucosidase and α-amylase enzymes is one of the significant approaches in designing anti-diabetic drugs because of its role in decreasing the carbohydrate digestion. In the present study we designed a new series of benzofuran Schiff base and evaluated them for their inhibitory potentials against α-amylase and α-glucosidase enzymes. Compounds 1–22 exhibited a varying degree of inhibitory activity with IC50 value ranging from 1.10 ± 0.10 to 24.60 ± 0.70 µm for α-amylase and 1.40 ± 0.10 to 24.00 ± 0.70 µm for α-glucosidase when compared with the standard drug acarbose having an IC50 value of 11.50 ± 0.30 and 12.20 ± 0.30 µm for α-amylase and α-glucosidase respectively. The most potent analogue among the series was analogue 12 having IC50 value of 1.10 ± 0.10 µm for α-amylase and 1.40 ± 0.10 µm for α-glucosidase. Similarly, analogues 1, 8 and 19 were also identified as potent analogues having IC50 values of 2.20 ± 0.10, 2.10 ± 0.10 and 2.10 ± 0.10 for α-amylase and 2.70 ± 0.10,1.90 ± 0.10 and 2.50 ± 0.10 for α-glucosidase respectively. Analogues 11( = 4.70 ± 0.10, 4.40 ± 0.10), 17 (IC50 = 5.20 ± 0.10, 5.70 ± 0.10) and 22 ( = 4.80 ± 0.10, 4.50 ± 0.10) exhibited moderate inhibition. Structure-activity relationship (SAR) of this series has been established which is mainly based on the position and nature of substituent on phenyl ring. In order to analyze the mode of inhibition of these compounds docking studies were carried out. Binding mode analysis of the most active inhibitors showed that these are well accommodated into the binding site of enzyme. © 2022 Elsevier B.V.