α-Glucosidase is a critical enzyme associated with diabetes mellitus, and the inhibitors of the enzyme play important roles in the treatment of the disease. In this study, the inhibitory effect and mechanism of rifampicin on α-glucosidase were investigated by multispectroscopic methods along with molecular docking technique. The results showed that rifampicin inhibited α-glucosidase activity prominently (IC50 = 135 ± 1.2 μM) in a reversible and competitive-type manner. The fluorescence intensity of α-glucosidase was quenched by rifampicin through forming rifampicin-α-glucosidase complex in a static procedure. And the formation of the rifampicin-α-glucosidase complex was driven spontaneously by hydrophobic forces and hydrogen bonds. The results obtained from molecular docking further indicated that hydrophobic forces were formed between rifampicin and amino acid residues Phe 173, Pro151, and hydrogen bonds were generated by the interactions of rifampicin with residues Ser 180, Asn 414, Gly160, and Gly161 of α-glucosidase. Moreover, it was found that the binding of rifampicin to α-glucosidase could alter the conformation of the enzyme to make it steady, and the binding distance was estimated to be 1.02 nm. Therefore, this study confirmed a novel α-glucosidase inhibitor and possibly contributed to the improvement of newfangled anti-diabetic agent.

A new facile method was developed for simple green synthesis of methylene-bridged phloroglucinol oligomers using nonthermal dielectric barrier discharge (DBD) plasma in methanolic solution. The chemical structures of these newly generated oligomers 2-5 were determined by interpretation of the spectroscopic data, and the inhibitory activity toward α-glucosidase of all isolates was evaluated. The unusual phloroglcuinol pentamer 5 connected by four methylene linkages showed a much higher potential inhibitory effect against α-glucosidase than the other generated oligomers 2-4 and appeared to be a promising lead for development as a potential antidiabetic agent.

Two new diphenyl ethers (1 and 2) and four new phenolic bisabolane sesquiterpenoids (3⁻6), together with five known related derivatives, were isolated from the culture of the endophytic fungus Aspergillus flavus QQSG-3 obtained from a fresh branch of Kandelia obobata, which was collected from Huizhou city in the province of Guangdong, China. The structures of compounds 1⁻6 were determined by analyzing NMR and HRESIMS data. The absolute configurations of 5 and 6 were assigned by comparing their experimental ECD spectra with those reported for similar compounds in the literature. All isolates were evaluated for their α-glucosidase inhibitory activity, of which compounds 3, 5, 10, and 11 showed strong inhibitory effects with IC50 values in the range of 1.5⁻4.5 μM.

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Recently, exploitation of nanozymes for signal amplification has aroused extensive research interesting in the fields of analytical chemistry and nanoscience. Herein, we introduced a new sensing strategy based on the ascorbic acid (AA) precisely regulated Ag3PO4 nanozyme for signal amplification. AA can reduce the partial Ag+ on the surface of Ag3PO4 nano-particles to form Ag° particles and result in the formation of Ag°/Ag3PO4 heterostructure. Due to surface plasmon resonance (SPR), the Ag° particles in heterostructure can act as the co-catalysts to enhance the electron-hole separation and the interfacial charge transfer, leading to a highly efficient oxidase mimicking activity for catalyzing the oxidation of the substrate of 3,3,5,5-tetramethylbenzidine (TMB) under visible light. Impressively, the activity enhancement of Ag3PO4 nano-peroxidase was linearly depended on the AA concentrations. Based on this feature, we employed it for multiple biological detections. For example, L-ascorbic acid-2-O-α-D-glucopyranosyl (AAG) was designed for α-glucosidase substrate, which can be hydrolyzed by α-glucosidase and lead to AA release. Further, the signal of α-glucosidase activity can be efficiently enlarged by Ag3PO4 nanozyme. Taking advantages of the powerful signal amplification by Ag3PO4 nanozymes, we developed the multiple sensing assays for monitoring AA in rat brain microdialysates, detection of α-glucosidase activity and its inhibitors (anti-diabetic drugs). The assay allowed the ultrasensitive colorimetric detection of α-glucosidase inhibitor with an ultra-low detection limit of 10 nM, and a naked-eye detection of the inhibitor concentration as low as 1 μM. The sensing strategy based on AA precisely regulated Ag3PO4 nano-peroxidase provides a promising candidate platform for highly stable and efficient cascaded signal amplification in biosensing field.

Currently, the potential risk of atrial fibrillation associated with antihyperglycemic drug use has been a topic of considerable interest. However, it remains uncertain whether different classes of antihyperglycemic drug therapy are associated with the risk of atrial fibrillation risk. Here, we investigated the association between different classes of antihyperglycemic drugs and new-onset atrial fibrillation (NAF). A case-matched study was performed based on the National Health Insurance Program in Taiwan. Patients who had NAF were considered the NAF group and were matched in a 1:4 ratio with patients without NAF, who were assigned to the non-NAF group. Patients were matched according to sex, age, diabetes mellitus duration, index date, and Charlson Comorbidity Index score. We used multivariate logistic regression controlling for potential confounders to examine the association between different classes of antihyperglycemic drug use and the risk of NAF. Overall, we identified 2,882 cases and 11,528 matched controls for the study. After adjusting for sex, age, comorbidities, and concurrent medications, users of biguanides or thiazolidinediones were at a lower risk of developing NAF when compared with non-users (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71-0.95 and OR 0.72, 95% CI 0.63-0.83, respectively). In contrast, users of insulin were at a higher risk of developing NAF than were non-users (OR 1.19, 95% CI 1.06-1.35). Sulfonylureas, glinides, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were not associated with developing the risk of NAF. In conclusion, the use of biguanides or thiazolidinediones may be associated with a low risk of NAF, whereas insulin may be associated with a significant increase in the risk of NAF in patients with type 2 diabetes mellitus during long-term follow-up. Further prospective randomized studies should investigate which specific class of antihyperglycemic drug treatment for diabetes mellitus can prevent or postpone NAF.

The emphasis of previous studies has targeted the development of insulin mimic with little attention given to the development of metabolic enzyme inhibitors. Our focus is to synthesise nine o-hydroxy and p-nitro-azomethine analogues, investigate their digestive enzyme inhibitory capacity, as well as the antioxidant and antimicrobial activities. The substituted Schiff bases were analysed using thermal gravimetric analyser (TGA), X-ray diffractometer (XRD), nuclear magnetic resonance spectroscopy (NMR), elemental analyser, and Fourier-transform infrared spectroscopy (FT-IR). Determination of synthetic yield revealed that the o-hydroxy analogues produced the highest yield of ≥77.1% compared to p-nitro and unsubstituted analogues. Spectra study showed the presence of azomethine stretching vibration at 1698⁻1613 cm-1, proton signals at δ 8.46⁻9.81, and carbon signals at δ 145.95⁻159.53 ppm. Investigation into the thermal property indicated an elevated melting point for the o-hydroxy analogue, compared to the p-nitro derivative which showed high stability to heat. There are similarities in crystalline structure with few unique patterns suggesting different substituent group. The antioxidant activities of the substituted analogues registered low half maximal inhibitory concentration (IC50), with exception to the ferric reducing power; indicating that the Schiff bases are weak siderophores. All nine Schiff bases were bacteriostatic or fungistatic at the screened concentrations; however, the nitro-substituted analogues have an enhanced activity with Minimum Inhibitory Concentration (MIC) values of 0.03⁻2.54 µM. Both o-hydroxy and p-nitro-substitution does not improve the antifungal activity of the compounds against A. niger. The o-hydroxyl and p-nitro Schiff base derivatives showed enhanced activity towards the inhibition of α -amylase and α-glucosidase by hydroxylation and glycosylation, respectively. Although, hydroxy derivatives of sulphonic acid derived Schiff base slightly decreased the activities on α-glucosidase and α-amylase. Our findings suggest that p-nitro substitution enhances the in vitro nonenzymatic activity while the o-hydroxy derivatives are good hydrolase inhibitors. Therefore, substituent modification can be used as an enhancement technique in designing novel pharmacophore.

Diabetes a non-communicable disease occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicated an increase in the trend of people diagnosed with type 2 diabetes mainly due to unhealthy life style. Here in we report a new class of oxindole derivatives 6a-kvia scaffold hopping of known α-glucosidase inhibitors 1-4. When molecular docking was performed against a homology model of α-glucosidase the resulting compound 6d revealed binding interactions comparable to 1-4. The compounds were accessed through a unique condensation-ring opening protocol of pyridofuranone building blocks. Overall the compounds exhibited decent binding to the yeast α-glucosidase, where the most potent compound 6h, inhibited the enzyme with IC50 of 0.6 µM. This was nearly threefold improvement from the original known compounds 1-4, selected to design the newer analogs. The reaction kinetics of 6h indicated competitive inhibition.