Synthesis, bioactivity, and molecular docking of benzimidazole-2-carbamate derivatives as potent -glucosidase inhibitors

Since time immemorial, diabetes has claimed countless lives throughout the world, and hundreds of mil-lions of people across the globe endure this chronic metabolic disorder with perpetual health compli-cations. Hence, specialists in medicinal and bioorganic chemistry are continually invigorated to design and synthesize alpha-glucosidase inhibitors that could potentially act as antidiabetic agents. To this end, in this work we have produced a series of variously substituted piperazin-1-yl benzimidazole-2-carbamates (7a-f) from multistep reactions in experimental yields ranging from moderate to relatively high. Sub-sequent to chemical identification with HRMS and spectroscopic elucidation using NMR and vibrational spectroscopic techniques, 15 derivatives were investigated for potential alpha-glucosidase inhibitory behavior. All, but 7a-1 , exhibited higher inhibition (IC50: 118-742 mu M) than acarbose (IC50: 759 mu M), the standard alpha-glucosidase inhibitor. The most effective inhibitors in this series were 7d-1 and 7f-2 with IC50 values of 118 and 155 mu M, respectively. Kinetic studies demonstrated that 7d-1 is a competitive inhibitor of alpha- glucosidase. Molecular docking was employed to provide insight into the interactions of these bioactive organic molecules with the amino acid residues at the active site of the foregoing enzyme.(c) 2023 Published by Elsevier B.V.