Background: Glucokinase activators (GKAs) are the new class of candidate drugs which
act on glucokinase (GK) enzyme and show their hypoglycaemic activity.
Objective: The present work was planned to synthesize and evaluate the antidiabetic activity of a series
of newer benzamide derivatives as potential GKAs.
Method: This work involved synthesis of newer benzamide derivatives from benzoic acid and their
evaluation by docking studies to determine the binding interactions for the best fit conformations in
the binding site of GK enzyme. Based on the results of docking studies, the selected molecules were
tested for their antidiabetic activity in the animal model.
Results: Amongst the synthesized molecules, compounds 14 and 20 with phenyl-substituted thiazole
moiety on amide nitrogen, exhibited highest activity in vivo. The results of the in vivo antidiabetic
studies were found to be consistent with those of docking studies.
Conclusion: These newly synthesized molecules thus can be treated as the initial hits for the development
of new, safe, effective and orally bioavailable GKAs as therapeutic agents for the treatment
of diabetic disorders.