Synthesis, Molecular Docking Studies and ADME Prediction of Some New Albendazole Derivatives as α-Glucosidase Inhibitors

Abstract

A series of novel 2-(substituted arylidene)-N-(5-(propylthio)-2,3-dihydro-1H-benzo[d]imidazol-2-yl)hydrazine-1-carboxamide derivatives 3a–i were synthesized via condensation of N-(5-(propylthio)-1H-benzo[d]imidazol-2-yl) hydrazinecarboxamide (2), with the corresponding ketone or aldehydes. The chemical structures of the compounds prepared were confirmed by analytical and spectral data. The compounds were screened for their α-glucosidase inhibitory activity and all of them showed better inhibition than acarbose, except 3h. In particular, compound 3a proved to be the most active compound among all synthetic derivatives having IC50 value 12.88±0.98 μM. Also, molecular docking studies were carried out for the compounds to figure out the binding interactions. Compound 3a has exhibited the highest binding energy (ΔG = –9.4 kcal/mol) and the most hydrogen bond interactions with active sites. Eventually, in silico studies were in good agreement with in vitro studies.

Keywords

• benzimidazoles
• albendazole
• semicarbazones
• antidiabetics
• α-glucosidase
• docking studies.