Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

•A novel method has been developed for the facile and efficient synthesis of imidazole derivatives.•This simple and versatile protocol yielded the targeted compounds in good to excellent yields.•Most of the synthesized compounds have exhibited potent α-glucosidase activity.•Generally ortho-hydroxy phenyl substituted compounds showed more promising inhibition.•Compound 3c presented the highest inhibitory activity with IC50 value 74.32 ± 0.59 μM.

A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a–3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-glucosidase inhibition at low micro-molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho-hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32 ± 0.59 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide