An efficient acid catalyzed methodology has been employed to synthesize a variety of aza-flavanones and their α-glucosidase inhibitory activity is evaluated using acarbose, miglitol and voglibose as reference standards. Molecular modeling studies were performed for all compounds to identify the important binding modes responsible for the inhibition activity of α-glucosidase which helped find key interactions between the enzyme and the active compounds. Among all the compounds 5g, 5r and 5w have shown high α-glucosidase inhibition activity compared to standard reference drugs and have been identified as promising potential antidiabetic agents. This study is the first biological evaluation of aza-flavanones as α-glucosidase inhibitors.

A series of novel thiazolidine-2,4-dione or rhodanine derivatives (5a-5k, 6a-6k) were synthesized and evaluated for their α-glucosidase inhibitory activity. The majority of compounds exhibited potent inhibitory activity in the range of 5.44 ± 0.13 to 50.45 ± 0.39 μM, when compared to the standard drug acarbose (IC50 = 817.38 ± 6.27 μM). Among the compounds in the series, compounds 5k, 6a, 6b, 6e, 6h and 6k showed potent inhibitory potential with IC50 values of 20.95 ± 0.21, 16.11 ± 0.19, 7.72 ± 0.16, 7.91 ± 0.17, 6.59 ± 0.15 and 5.44 ± 0.13 μM, respectively. Compound 6k (IC50 = 5.44 ± 0.13 μM), containing chloro and rhodanine groups at the 2- and 4-positions of the phenyl ring respectively, was found to be the most active compound that inhibits α-glucosidase activity. Furthermore, molecular docking studies were performed to understand the binding interactions between the molecule and enzyme.

Postprandial hyperglycemia can be controlled by delaying the absorption of glucose resulting from carbohydrate digestion. α-Amylase is the initiator of the hydrolysis of polysaccharides, and therefore developing α-amylase inhibitors can lead to development of new treatments for metabolic disorders like diabetes mellitus. In the present work, we set out to rationally develop α-amylase inhibitors based on the thiazolidine-4-one scaffold. The structures of all these newly synthesized hybrids were confirmed by spectroscopic analysis (IR, 1H-NMR, MS). The appearance of two sets of signals for some protons in 1H NMR revealed the existence of a mixture of 2E,5Z (37.1-42.0%) and 2Z,5Z isomers (58.4-62.8%), which was further supported by DFT studies. All the newly synthesized compounds have potential inhibitory properties as revealed through in vitro α-amylase inhibition activity. Compound 5a at 100 μg mL-1 concentration showed a remarkable inhibition of 90.04%. In vitro α-amylase inhibition was further supported by docking studies of compound 5a against the active site of human pancreatic α-amylase (PDB ID: ; 2QV4). The docking studies revealed that the bonding interactions found between 5a and human pancreatic α-amylase are similar to those responsible for α-amylase inhibition by acarbose.

Current antiobesity and antidiabetic tools have been insufficient to curb these diseases and frequently cause side effects; therefore, new pancreatic lipase and α-glucosidase inhibitors could be excellent aids for the prevention and treatment of these diseases. The aim of this study was to identify, quantify, and characterize the chemical compounds with the highest degree of inhibitory activity of these enzymes, contained in a Ludwigia octovalvis hydroalcoholic extract. Chemical purification was performed by liquid-liquid separation and column chromatography. Inhibitory activities were measured in vitro, employing acarbose, orlistat, and a Camellia sinensis hydroalcoholic extract as references. For structural elucidation, Nuclear Magnetic Resonance was carried out, and High Performance Liquid Chromatography was used to quantify the compounds. For α-glucosidases, L. octovalvis hydroalcoholic extract and its ethyl acetate fraction showed half-maximal Inhibitory Concentration (IC50) values of 700 and 250 μg/mL, for lipase, 480 and 718 μg/mL, while C. sinensis showed 260 and 587 μg/mL. The most active compounds were identified as ethyl gallate (1, IC50 832 μM) and gallic acid (2, IC50 969 μM); both displayed competitive inhibition of α-glucosidases and isoorientin (3, IC50 201 μM), which displayed uncompetitive inhibition of lipase. These data could be useful in the development of a novel phytopharmaceutical drug.

Objective: Recent studies have suggested that metformin can penetrate the blood-brain barrier, protecting neurons via anti-inflammatory action and improvement of brain energy metabolism. In this study, we aim to investigate the effect of metformin on cognitive function in patients with abnormal glucose metabolism and non-dementia vascular cognitive impairment (NDVCI). Methods: One hundred patients with NDVCI and abnormal glucose metabolism were randomly allocated into two groups: metformin and donepezil (n = 50) or acarbose and donepezil (n = 50). The neuropsychological status, glucose metabolism, and common carotid arteries intima-media thickness (CCA-IMT) before and after a year of treatment, were measured and compared between the groups. Results: Ninety four patients completed all the assessment and follow-up. After a year of treatment, there was a decrease in Alzheimer's disease Assessment Scale-Cognitive Subscale scores and the duration of the Trail Making Test in the metformin-donepezil group. Furthermore, these patients showed a significant increase in World Health Organization-University of California-Los Angeles Auditory Verbal Learning Test scores after treatment (all P < 0.05). However, there was no obvious improvement in cognitive function in the acarbose-donepezil group. We also observed a significant decrease in the level of fasting insulin and insulin resistance (IR) index in the metformin-donepezil group, with a lower CCA-IMT value than that in the acarbose-donepezil group after a year of treatment (P < 0.05). Conclusion: We conclude that metformin can improve cognitive function in patients with NDVCI and abnormal glucose metabolism, especially in terms of performance function. Improved cognitive function may be related to improvement of IR and the attenuated progression of IMT. Trial Registration: ChiCTR-IPR-17011855.

Treatment of type 2 diabetes is achieved through the inhibition of carbohydrate hydrolyzing enzymes such as α-glucosidase and α-amylase. The present study was conducted to identify novel α-glucosidase inhibitory peptides and to validate the α-glucosidase and α-amylase inhibitory activities of two promising candidates. A total of 4210 potential α-glucosidase inhibitory peptides with 3-5 amino acid residues were designed and individually subjected to in silico simulated gastrointestinal (GIT) digestion using the BIOPEP database. Subsequently, 844 GIT resistant peptides were then subjected to molecular docking using Autodock Vina to determine their binding free energy against human α-glucosidase (PDB ID: 3L4Y). Among all the peptides, SVPA and SEPA were found to have the lowest binding free energies of -8.7 and -8.6 kcal/mol, respectively. Docking of SVPA and SEPA on human α-amylase (PDB ID, 4GQR) identified that both peptides also bind to α-amylase with binding energies of -6.5 and -6.9 kcal/mol, respectively. Hydrogen bond interactions were critical for the binding of both peptides to the α-glucosidase and α-amylase. In vitro, SVPA and SEPA inhibited α-glucosidase and α-amylase activities with IC50 values several fold lower than acarbose except for SVPA that had a significantly higher (p <  0.05) IC50 value than acarbose against α-glucosidase. Lineweaver-Burk analyses revealed that SVPA was an uncompetitive inhibitor of the two enzymes, while SEPA inhibited α-glucosidase and α-amylase non-competitively and uncompetitively, respectively. This study has identified two novel and active α-glucosidase inhibitory peptides that could resist GIT digestion and therefore, have the potential to retard postprandial hyperglycemia in diabetic patients.

α-Glucosidase inhibitors (aGIs) have been used as an effective therapy for type-2 diabetes, which remains a global health issue. The aim of this study was to achieve bioactivity-guided isolation, identification and evaluation of hypoglycemic compounds from Euonymus laxiflorus Champ. trunk bark (ELCTB). Eleven active compounds were isolated and identified as walterolactone A/B β-d-pyranoglucoside (1), 1-β-d-glucopyranosyloxy-3,5-dimethoxy-4-hydroxybenzene (9), (-)-gallocatechin (10), schweinfurthinol 9-O-β-d-pyranoglucoside (11), 1-O-(3-methyl)-butenoyl-myo-inositol (12), leonuriside (14), (+)-catechin (19), methyl galloate (20), (-)-catechin (23), and condensed tannins (5 and 18). Of these 11, novel 4 compounds (1, 11, 12, and 14) were found as new α-glucosidase inhibitors. Notably, in vitro results indicated that compounds 1, 5, 10⁻12, 18, and 19 showed potent activity (IC50 = 0.076-31 µg/mL), and their activities were at a higher level than that of acarbose, a commercial inhibitor (IC50 = 1345 µg/mL). In animal tests, the major inhibitor, condensed tannin (18), demonstrated significant reduction of plasma glucose in mice with no symptoms of diarrhea at the dose of 100 mg/kg bw. The results suggest that Euonymus laxiflorus Champ. is a rich source of bioactive compounds for development as health food or drugs with potent hypoglycemic effect. The results of this study also enriched the current novel biological activities of constituents from Euonymus laxiflorus species.

An ultrasensitive fluorometric assay is described for the determination of the activity of the enzyme α-glucosidase in waters and living cells. Carbon dots doped with nitrogen and boron (N,B-CDs) were prepared that have excitation/emission peaks at 400/510 nm and a fluorescence quantum yield of 47%. 4-Nitrophenylglucoside is added and then hydrolyzed by α-glucosidase to form yellow 4-nitrophenol which screens off fluorescence due to an inner filter effect. The method was applied to the determination of α-glucosidase activity and has a 3 mU mL-1 detection limit. It was subsequently applied to the determination of the α-glucosidase inhibitor acarbose which can be determined in a concentration as low as 10 nM (at three times the standard deviation versus slope). The method was also applied to the determination of α-glucosidase activity and acarbose in living HeLa cells and MCF-7 cells. The method is simple, sensitive, and excellently selective. Graphical abstract N,B-CDs as ultrasensitive fluorescence probe for α-glucosidase activity and its inhibitor in waters and living cells based on IFE.