A Structure—Activity Relationship Study of the Inhibition of α-Amylase by Benzoic Acid and Its Derivatives

Abstract

Phenolic acids are widely found in fruits and vegetables. The inhibitory effect of phenolic acids on α-amylase, a key enzyme for starch digestion, has attracted the attention of researchers. To further investigate the effects of different substituents on the benzene ring of phenolic acid on the inhibition of α-amylase activity, in vitro experiments and molecular docking were used. The structure-activity relationships of 17 phenolic acids with benzoic acid as the parent nucleus were analyzed by determining their half inhibitory concentration (IC50) toward α-amylase. The results showed that 2,3,4-trihydroxybenzoic acid had the strongest inhibitory effect on α-amylase with an IC50 value of 17.30 ± 0.73 mM. According to the structure-activity analysis, the hydroxyl group at the 2-position on the benzene ring had a strong positive effect on the inhibitory activity of α-amylase, while methoxylation at the 2-position and hydroxylation at the 5-position had a negative effect. Molecular docking revealed that hydrogen bonding and hydrophobic interactions were involved in the inhibition, with hydrogen bonding being the primary force. These findings provide a more comprehensive understanding of phenolic acids as inhibitors of α-amylase and provide new ideas for the design of dietary formulations for diabetic patients.

Phenolic profiles and in vitro biochemical properties of Thai herb ingredients for chronic diseases prevention

“…BM exhibited the second most abundant TPCs, with high levels of phenolic acids including gallic acid and 3,4-dihydioxybenzoic acid, moderate amounts of flavonoids including luteolin and naringenin detected by LC–ESI–MS/MS. As the most abundant phenolic detected in BM, gallic acid inhibited α-amylase with IC 50 ranging 4.35–13.69 mM depending on the assay method 35 , while another study indicated that 3,4-dihydroxybenzoic acid exhibited a similar IC 50 value to gallic acid 36 . When compared to acarbose, a commercially available T2DM drug acting as an α-amylase and α-glucosidase competitive inhibitor, gallic acid and 3,4-dihydroxybenzoic acid were less effective, with IC 50 ranging 0.018–0.300 mM against α-amylase 35 .…”

Potential anti‐obesity effect of saponin metabolites from adzuki beans: A computational approach

“…Three core amino acids featured the conserved catalytic residues in α‐amylase, Glu 233, Asp 197, and Asp 300 (Williams et al., 2015 ). Upon inspecting the 2D and 3D interactions of adzukisaponins inside the binding groove, these residues were detected forming clear ionic hydrogen bond interactions both directly and mediated by water molecules intrinsic to the protein pocket (Guan et al., 2022 ).…”

Phenolic content of Thai Bao mango peel and its in-vitro antioxidant, anti-cholinesterase, and antidiabetic activities

“…Similarly, Gondi et al (2015) examined the glucose-lowering potential of MP powder in diabetic rats and noted that supplementation of 5 % and 10 % MPP in the diet lowered oxidative stress along with a remarkable reduction in the serum glucose level and other associated parameters. It was evident that α-amylase and α-glucosidase are prone to a wide range of polyphenols, for instance, 3,4- hydroxybenzoic acid ( Guan et al, 2022 ) and mangiferin ( Santos et al, 2022 ), as the unique nature of these phenolic compounds makes them have an affinity to bind with digestive enzymes like α-glucosidase. A significant concentration of these compounds has been detected in the present study, which could have resulted in α-glucosidase and α-amylase inhibition.…”