Unravelling the Potential of Trisubstituted Imidazole Derivatives to Combat Hyperglycemia: An In vitro and In silico Approach

Molecules containing imidazole possess a diverse array of pharmacological activities. Recently, a new library of 2,4,5-trisubstituted imidazoles was synthesised in our previous study utilising a novel organocatalyzed synthetic pathway. Further, these molecules were screened for in vitro enzymatic activity against target α-glucosidase at different concentrations (0–1000µg/mL) of trisubstituted imidazoles. The absorbance was measured at 405 and 540nm using a multiplate reader, and the percentage of α-glucosidase inhibitory activity with the IC 50 values of 2,4,5-trisubstituted imidazoles was calculated. Among them, compounds 3a, 3b, and 3e were found to have good α-glucosidase inhibition with an IC 50 of 4.8, 5.3, and 4.3μg/mL, respectively, when compared to the standard drug acarbose. Additionally, molecular docking studies were performed to comprehend the molecular interaction between the molecule and imidazole-sensitive hypoglycemic target α-glucosidase (PDB: 3WY1). The majority of 2,4,5-trisubstituted imidazoles showed better binding energy (-7.4 to -8.2Kcal/mol) with the binding pockets of α-glucosidase. Swiss ADME was employed to predict the adsorption, distribution, metabolism, and elimination properties of the synthesised compounds.