Synthesis of 6-hydroxyaurone analogues and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity: Development of highly active 5,6-disubstituted derivatives

Abstract A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro α-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of α-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC 50  = 50.30 μM). Surprisingly, analogues devoid of a substituent at C-2 but having an aryl group at C-5 were found to be highly active (e.g., 7f , IC 50  = 9.88 μM). Docking analysis substantiated these findings. The kinetic analysis of compound 7f , the most potent α-glucosidase inhibitor of this study, revealed that it inhibited α-glucosidase in an irreversible and mixed competitive mode. In addition, compounds 7f and 10c exhibited significant glucose consumption promoting activity at 1 μM.