Synthesis of activity evaluation of flavonoid derivatives as ɑ-glucosidase inhibitors

Abstract

Six flavonoid derivatives were synthesized and tested for anti-α-glucosidase activities. All derivatives were confirmed using NMR and HRMS and exhibited excellent inhibitory effects on α-glucosidase. Derivative four exhibited the highest anti-α-glucosidase activity (IC50: 15.71 ± 0.21 μM). Structure-activity relationship results showed that bromine group would be the most beneficial group to anti-α-glucosidase activity. Inhibitory mechnism and inhibition kinetics results showed derivative four was a reversible and mixed-type inhibitor. Molecular docking revealed that derivative four was tightly bind to the amino acid residues of active pocket of α-glucosidase and formed hydrogen bond, π-π stacking, and Pi-Donor hydrogen with α-glucosidase. Moreover, the physicochemical parameters of all derivatives were assessed using SwissADME software. This results also showed that the hybridization of flavonoid and phenylpropionic acid would be a useful strategy for the development of α-glucosidase inhibitors.

Thymus Species from Romanian Spontaneous Flora as Promising Source of Phenolic Secondary Metabolites with Health-Related Benefits

“…The bioactive potential of the studied species was influenced by their chemical profile, especially for the anti-glucosidase and antimicrobial effects. The inhibition of α-glucosidase was higher for the extracts rich in flavonoids, which is in line with previous obtained results regarding the ability of these plant metabolites to act as potential antidiabetic agents [62,63]. As one of the therapeutic targets in diabetes mellitus is this enzyme, the research for novel α-glucosidase inhibitors has intensified in recent years, with several potent candidates being found among the flavonoids group.…”

“…Tadera et al [62] studied the anti-glucosidase properties of different isolated flavonoids, revealing elevated inhibition rates for the flavonol-type (i.e., quercetin-91%) and flavone-type (i.e., luteolin-92%) derivatives. Moreover, using natural flavonoids as scaffolds, Zhu et al [63] obtained several compounds through chemical synthesis with augmented anti-glucosidase potential and improved binding activity to the active site of the enzyme. Of course, the antidiabetic potential of several thyme species (i.e., T. spicata var.…”

Spermacoce alata Aubl. Essential Oil: Chemical Composition, In Vitro Antioxidant Activity, and Inhibitory Effects of Acetylcholinesterase, α-Glucosidase and β-Lactamase

“…Diabetes mellitus (DM) is a common chronic metabolic disorder characterized by hyperglycemia caused by the disturbance of carbohydrate metabolism [ 13 ]. α-Glucosidase is a key glucoside hydrolase that catalyzes the hydrolysis of disaccharides and oligosaccharides into absorbable monosaccharides in the final step of carbohydrate digestion [ 14 , 15 ].…”