RESUMO
Gallotannins are phenolic natural products containing galloyl moieties connected to polyhydric alcohol cores, e.g., D-glucose. Some gallotannins are reported to have antidiabetic properties, such as α-glucosidase inhibitory activity. In this study, fourteen unnatural gallotannin derivatives with 1,5-anhydroalditol and inositol as the cyclic polyol cores were synthesized to investigate how their structures affected antioxidative and α-glucosidase inhibitory activities. Tannic acid demonstrated the most potent antioxidative activity (EC50 = 2.84 µM), with potency increasing proportionally to the number of galloyl moieties. Synthetic inositol derivatives outperformed 1,5-anhydroalditol derivatives in rat α-glucosidase inhibitory activity. Pentagalloyl glucose, a natural compound, demonstrated the highest activity (IC50 = 0.336 µM).
Assuntos
Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Taninos Hidrolisáveis/farmacologia , alfa-Glucosidases/metabolismo , Animais , Antioxidantes/síntese química , Antioxidantes/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Compostos de Bifenilo/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/química , Taninos Hidrolisáveis/síntese química , Taninos Hidrolisáveis/química , Conformação Molecular , Picratos/antagonistas & inibidores , RatosRESUMO
Twenty-one natural and unnatural phenolic compounds containing a carbohydrate moiety were synthesized and their structure-activity relationship (SAR) was evaluated for α-glucosidase inhibition and antioxidative activity. Varying the position of the galloyl unit on the 1,5-anhydro-d-glucitol (1,5-AG) core resulted in changes in the α-glucosidase inhibitory activity and notably, particularly strong activity was demonstrated when the galloyl unit was present at the C-2 position. Furthermore, increasing the number of the galloyl units significantly affected the α-glucosidase inhibition, and 2,3,4,6-tetra-galloyl-1,5-AG (54) and 2,3,4,6-tetra-galloyl-d-glucopyranose (61) exhibited excellent activities, which were more than 13-fold higher than the α-glucosidase inhibitory activity of acertannin (37). Moreover, a comparative structure-activity study suggested that a hemiacetal hydroxyl functionality in the carbohydrate core and a biaryl bond of the 4,6-O-hexahydroxydiphenoyl (HHDP) group, which are components of ellagitannins including tellimagrandin I, are not necessary for the α-glucosidase inhibitory activity. Lastly, the antioxidant activity increased proportionally with the number of galloyl units.
