Synthesis of Novel Methylsulfonylacrylimidamide via Click Chemistry Approach, Computational Analysis and α‐ Glucosidase Inhibition Activity

A series of Novel Methylsulfonylacrylimidamide analogs ( 4 a – 4 h ) were designed, synthesized, and screened for their α ‐glucosidase inhibitory activity. The results indicated that some of the synthesized derivatives displayed inhibitory activities against α ‐glucosidase with IC 50 values ranging from 10.35±0.15 to 60.39±1.77 μM when compared to standard drug acarbose (IC 50 832.22±2.00 μM). Among the synthesized derivatives, compounds 4 f and 4 h with a Di cyclohexyl and dioctyl substitution in the acrylimidamide displayed the most significant inhibitory activity with the IC 50 value of 14.54±0.19 μM and 10.35±0.15 μM. The inhibitory action of compounds 4 f and 4 h against α ‐glucosidase was studied by enzyme kinetic and molecular docking. In vitro , cytotoxicity showed that 4 f and 4 h exhibited low cytotoxicity against human cell lines. The ADME study suggested that most compounds will likely be orally active as they obeyed Lipinski's rule of five. Our studies showed that these derivatives could be considered a new class of α ‐glucosidase inhibitors.