Synthesis, In-Vitro, and In-silico analysis of Repurposed Substituted 2,7-Dimethylimidazo [1,2-a]Pyridine-3-Carboxamide based α-Amylase inhibitors via docking, MMGBSA, dynamics simulation techniques and pharmacokinetic evaluation
TL;DR
In-silico ADME studies indicated favorable pharmacokinetic properties, including high gastrointestinal absorption, low TPSA, BBB permeability, and compliance with Lipinskis rule, while toxicity prediction suggested acceptable safety profiles for the synthesized derivatives, highlighting their potential as promising α-amylase inhibitory candidates.
Abstract
A series of substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide derivatives (Va)-(Vm) was evaluated for α-amylase inhibitory activity, where compounds (Vg; IC 50 = 197.5 µg/mL), (Vd; IC 50 = 204.4 µg/mL), and (Vk; IC50 = 207.6 g/mL) demonstrated promising inhibitions compared with the standard acarbose (reported, IC 50 = 66.65 µg/mL). Molecular docking revealed strong binding affinities (-7.4 to -8.7 kcal/mol), with compound (Vg) showing the best affinity profile through hydrophobic, hydrogen-bonding, π-stacking, halogen, and π-cation interactions with key active-site residues, further supported by stable 100 ns molecular dynamics simulation. In-silico ADME studies indicated favorable pharmacokinetic properties, including high gastrointestinal absorption, low TPSA, BBB permeability, and compliance with Lipinskis rule, while toxicity prediction suggested acceptable safety profiles for the synthesized derivatives, highlighting their potential as promising α-amylase inhibitory candidates.