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 (3a and 3b) 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 3a and 3b retarded both maltase and sucrase via a non-competitive mechanism.