Investigation of the structure-activity relationship of resveratrol and its glycosylated and acylated derivatives in relation to their α-glucosidase inhibitory activities

Abstract

Resveratrol with excellent α-glucosidase inhibitory activity is widely distributed in foods. However, in-depth research on the effects of glycosylation and acylation of resveratrol on its α-glucosidase inhibitory activity is limited. In the present study, we investigated the structure-activity relationship of resveratrol, resveratrol-4’- O -glucoside, resveratrol 4’- O -(6′′- O -galloyl)-glucoside and resveratrol 4’- O -(2′′- O -galloyl)-glucoside against α-glucosidase. Notably, C-4′ glycosylation enhanced potency, and subsequent galloyl acylation further improved activity with acylation at C-6′′ slightly outperforming that at C-2′′. Spectroscopic analyses confirmed conformational changes in the enzyme upon binding. Molecular docking showed C-4′ glycosylation led to the formation of additional hydrogen bonds with α-glucosidase, and subsequent acylation further increased their number. Molecular dynamics simulations showed resveratrol 4’- O -(6′′- O -galloyl)-glucoside, owing to its lower steric hindrance than resveratrol 4’- O -(2′′- O -galloyl)-glucoside, penetrates more deeply into the active-site pocket of α-glucosidase, resulting in a more stable binding. These findings may provide theoretical basis for the development of resveratrol and its derivatives in functional foods. • Glycosylation at the C-4′ of resveratrol significantly enhanced its α-glucosidase inhibitory activity. • Galloylation at C-6′′ or C-2′′ of resveratrol-4’-O-glucoside enhanced its α-glucosidase inhibitory activity. • Galloylation at C-6′′ of resveratrol-4’-O-glucoside forms more conventional H-bonds than 2″ form, enhancing α-glucosidase binding stability. • Galloylation at C-6′′ of resveratrol-4’-O-glucoside binds slightly better to α-glucosidase active site than 2″ form.

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