Cannabinol derivatives, a new series of α-glucosidase inhibitors: synthesis, structure–activity relationship, and kinetic study

A new series of cannabinol derivatives was synthesised and assessed for their inhibitory effects against α-glucosidase. Of nineteen derivatives evaluated, the brominated analogues (<b>3a</b> and <b>3b</b>) demonstrated the most potent inhibition against rat intestinal α-glucosidase. Structure-activity relationship analysis suggested that the phenolic hydroxy group and the introduced bromine atoms play crucial roles in enhancing inhibitory potency. Enzyme kinetic studies further revealed that <b>3a</b> and <b>3b</b> retarded both maltase and sucrase <i>via</i> a non-competitive mechanism.