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

A series of 6-hydroxyaurones and their analogues have been synthesized and evaluated for their in vitro alpha-glucosidase inhibitory and glucose consumption-promoting activity. These compounds exhibited varying degrees of alpha-glucosidase inhibitory activity, 11 of them showing higher potency than that of the control standard acarbose (IC50 = 50.30 mu M). 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, IC50 = 9.88 mu M). Docking analysis substantiated these findings. The kinetic analysis of compound 7f, the most potent alpha-glucosidase inhibitor of this study, revealed that it inhibited alpha-glucosidase in an irreversible and mixed competitive mode. In addition, compounds 7f and 10c exhibited significant glucose consumption promoting activity at 1 lM. (C) 2017 Elsevier Ltd. All rights reserved.