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

Inhibition of alpha-glucosidase and oz-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 alpha-amylase and alpha-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 mu m for alpha-amylase and 1.40 +/- 0.10 to 24.00 +/- 0.70 mu m for alpha-glucosidase when compared with the standard drug acarbose having an IC50 value of 11.50 +/- 0.30 and 12.20 +/- 0.30 mu m for alpha-amylase and alpha-glucosidase respectively. The most potent analogue among the series was analogue 12 having IC50 value of 1.10 +/- 0.10 mu m for alpha-amylase and 1.40 +/- 0.10 mu m for alpha-glucosidase. Similarly, analogues 1, 8 and 19 were also identified as potent analogues having IC(50)values of 2.20 +/- 0.10, 2.10 +/- 0.10 and 2.10 +/- 0.10 for oz-amylase and 2.70 +/- 0.10,1.90 +/- 0.10 and 2.50 +/- 0.10 for alpha-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. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Inhibition of alpha-glucosidase and alpha-amylase enzymes is a significant approach in designing anti-diabetic drugs. A new series of benzofuran Schiff base compounds were designed and evaluated for their inhibitory potentials. The most potent analogues showed good accommodation in the enzyme's binding site.