Design, synthesis and biological evaluation of novel sulfonamide hydrazones as α-glucosidase and α-amylase inhibitors

Background and Aims: Diabetes mellitus is among the major hazards to global public health due to increasing incidence worldwide, and new therapeutic agents are urgently needed for the control of the disease. In this study, a novel series of sulfonamide hydrazones (3a-i) were synthesized and evaluated, in vitro, for α-amylase and α-glucosidase inhibitor activities. Methods: Target compounds were prepared according to a high-yielded synthetic route. The in vitro antidiabetic activity of the compounds was analyzed by evaluating the inhibitory abilities on α-glucosidase and α-amylase enzymes. Acarbose was chosen as a reference in this study. Results: Compounds 3d, 3e, 3g and 3h exhibited better α-glucosidase inhibitory activity compared to reference antidiabetic drug acarbose. Compound 3g was the most active analogue, possessing an IC50 value of 65.27 μg/mL. 3d, 3e, 3g and 3h showed similar α-amylase inhibitory activity compared to acarbose when tested at high concentrations. However, their IC50 values were much higher compared to that of reference acarbose. Conclusion: The most active analogue 3g was found to be two times more active than acarbose. The addition of a bulky group to the 4-position of the cyclohexane ring seemed to have a positive effect on antidiabetic activity. The new hydrazone derivatives reported in this study are potentially promising candidates for developing new antidiabetic agents.