Novel indole-sulfonamide hybrids as <i>α</i> -amylase and <i>α</i> -glucosidase inhibitors: a rational approach combining enzyme kinetics and <i>in silico</i> analysis

Abstract The development of effective α -amylase and α -glucosidase inhibitors is an important strategy for the management of type 2 diabetes mellitus. In the present study a series of novel indole-sulfonamide hybrids ( 1–17 ) were designed synthesized and evaluated for their inhibitory activity against α -amylase and α -glucosidase enzymes. The synthesized compounds were characterized through 1 HNMR, 13 CNMR and HREIMS. All analogs demonstrated promising enzyme inhibitory activity when compared with the reference drug acarbose. Among all tested compounds, analog 4 (IC 50 = 16.6, and 16.4 µM), 11 (IC 50 = 15.0 and 15.8 µM), 12 ( IC 50 = 14.0 and 14.1 µM), and 15 ( IC 50 = 12.1 and 13.7 µM) demonstrated good inhibitory potentials against α -amylase and α -glucosidase enzymes respectively. Enzyme kinetic studies revealed that the most active compounds ( 4, 11, 12 , and 15 ) acted as competitive inhibitors with Ki values ranging from 4.2 to 5.8 µM for α -amylase and 28.8–28.5 µM for α -glucosidase. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.