Α-glucosidase Inhibitors Research Articles

Synthesis and in vitro Biological Evaluation of a Series of 5-Benzylidene Derivatives of Rhodanine-Sulfonylurea Hybrid as a Novel Class of α-Glucosidase Inhibitors

A novel rhodanine-sulfonylurea hybrid (C) has been prepared based on the isocyanate-amine reaction conditions in the first step and its 5-benzylidene analogues (C1-C13) were synthesized using Knoevenagel reaction conditions as the subsequent step. The physical and spectral characterization of all the synthesized compounds (C-C13) was performed using FT-IR, 1H NMR and HR-ESI-MS spectral methods. All compounds were subjected to in vitro α-glucosidase enzyme inhibitory properties at 100 µM concentration. The results were compared with a standard drug, voglibose, also tested at the similar concentrations. The bioassay results revealed that the intermediate compound C was more potent with a percentage inhibitory activity of 64.86%, which is relatively better than the series of 5-benzylidene analogues (C1-C13) synthesized from the intermediate C. This clearly displayed that substitution at position-5 on the rhodanine ring of intermediate C is not a favourable substitution to enhance the bioactivity; however, one of the derivative compounds, C12, has exhibited potency of 58.32%, which is close to the compound C. It is significant that both the intermediate C and compound C12 displayed better potency compared to the standard voglibose, with percentage inhibition recorded at 37.75%. The additive or synergistic potential of the bioactive pharmacophore tosylurea, which was earlier established, tolerated the rhodanine ring substitution towards retaining the α-glucosidase inhibitory properties.

Phytochemical Analysis and Evaluation of Antioxidant, Antidiabetic, and Anti-inflammatory Properties of Aegle marmelos and Its Validation in an In-Vitro Cell Model.

Persistent hyperglycemia significantly increases oxidative stress and inflammation resulting in multiple cellular and molecular alterations which further exacerbate the diabetes associated complications.Aegle marmelos (L.) Corrêais a medicinal plant used in the Indian system of medicine for treating various disorders including diabetes. However, studies on phytoconstituents and their pharmacological activity of this plant are limited. Therefore, we aimed to determine the phytochemical components, evaluate the antidiabetic activity, anti-inflammatory activity, and antioxidant activity ofA. marmelosleaf extract, and validate its mechanistic effects in an in vitro cell model. The qualitative and quantitative analysis of the different phytoconstituents in the extract was determined using standardized protocols. The antioxidant activity of the extract was evaluated by 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay and ferric reducing antioxidant power (FRAP) assay. The antidiabetic activity of the extract was evaluated by α-amylase inhibition and α-glucosidase inhibition assay. The anti-inflammatory activity was studied using an albumin denaturation assay. In addition, the pharmacological effect(s) of leaf extract was checked in the normal rat kidney fibroblast cells (NRK-49F) under high glucose conditions. Intracellular reactive oxygen species (ROS) generation was measured by fluorometry using fluorescence probe 2',7'-dichlorodihydrofluorescin diacetate (DCF-DA). mRNA expression of inflammatory markers including inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) was studied using real-time quantitative polymerase chain reaction (RT-qPCR). Cell migration was studied using cell scratch assay. Statistical analysis was performed using GraphPad Prism version 8.0. The phytochemical analysis ofA. marmelosleaf extract revealed the presence of alkaloids, phenols, flavonoids, and saponins. The extract showed higher antioxidant activity in the DPPH (IC50=258.21 µg/mL) and FRAP assay (IC50=293.83 µg/mL). The extract exhibited prominent antidiabetic activity by inhibiting enzymes α-Amylase (IC50=73.2 µg/mL) and α-glucosidase (IC50=43.9 µg/mL). In addition, the extract showed effective anti-inflammatory activity by significantly inhibiting the denaturation of egg albumin (IC50=102.8 µg/mL). Further, the leaf extract significantly decreased the high glucose-induced ROS generation as well as inflammatory markers in rat fibroblast cell lines in a dose-dependent manner. Additionally, high glucose-induced cell migration as the measure of cell injury was effectively reduced by the extract treatment. A. marmelosleafextract was quantified to possess a substantial amount of important phytoconstituents that have promising pharmacological properties. Besides showing antidiabetic activity, the extract significantly combats the high glucose-induced ROS generation, inflammatory markers expressions, and cell migration. Further, in-depth studies and clinical trials are warranted so as to position these traditional remedies for the treatment of metabolic disorders.

Phenolic Compositions of Different Fractions from Coffee Silver Skin and Their Antioxidant Activities and Inhibition towards Carbohydrate-Digesting Enzymes.

Seeking food-derived antioxidants and inhibitors of α-glucosidase and α-amylase has been recognized as an effective way for managing diabetes. Coffee silver skin (CSS) is rich in phenolic compounds, which may be potential agents as antioxidants and for α-glucosidase and α-amylase inhibition. But whether phenolics in different forms show similar bioactivity remains unknown. In this study, phenolic compounds in CSS were extracted as free phenolics (FPs), esterified phenolics (EPs), and bound phenolics (BPs). The phenolic profiles and antioxidant activities of them were investigated. Their inhibitory effects on α-glucosidase and α-amylase were analyzed, and the inhibitory mechanisms were elucidated by molecular docking and molecular dynamic simulation. Results showed that FPs exhibited the best antioxidant ability and inhibitory effects on α-glucosidase and α-amylase. A total of 17 compounds were identified in FPs with 3-caffeoylquinic acid, 4-feruloylquinic acid, and dicaffeoylquinic acids as the dominant ones. Typical phenolics in FPs could bind to α-glucosidase and α-amylase through hydrogen bonds and form hydrophobic interaction with several key amino acid residues. In addition, 3,4-dicaffeoylquinic acid and 3-caffeoylquinic acid might be the principal components that account for the inhibitory effect of FPs on α-glucosidase. The results of this study may provide some scientific support for CSS utilization as a health-beneficial component in functional food development for type 2 diabetes mellitus management.

Bioassay Guided Isolation and α-Glucosidase Inhibition Studies of a New Sesquiterpene from Ochradenus aucheri.

The aim of the current study was to explore the anti-diabetic potential of Ochradenus aucheri Boiss (O. aucheri). All the fractions of O. aucheri were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor. The preliminary screening showed that all the fractions including n-hexane (38.0 ± 1.38 μg/mL), dichloromethane (92.6 ± 6.18 μg/mL), ethyl acetate (29.2 ± 0.51 μg/mL) and n-butanol (361.8 ± 5.80 μg/mL) displayed significant α-glucosidase inhibitory activity. The activity-directed fractionation and purification of ethyl acetate fraction led to the isolation of one new sesquiterpenoid, Jardenol (1), and two known metabolites: β-stitosterol-3-O-β-D-glucopyranoside (2) and β-Sitosterol (3). To the best of our knowledge, these metabolites have not been isolated from this plant previously. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. Compound 1 showed significant α-glucosidase inhibition with an IC50 value of 138.2 ± 2.43 μg/mL as compared to positive control acarbose (IC50 = 942.0 ± 0.60 μg/mL). Additionally, in-silico docking was employed to predict the binding mechanism of compound 1 in the active site of the target enzyme, α-glucosidase. The docking results suggested that the compound forms strong interactions at the catalytic site of α-glucosidase. The results of the present study indicated that the newly purified secondary metabolite, Jardenol, can be a promising anti-diabetic compound.

The structure elucidation, anti-aging and hypoglycemic effects of an O-acetyl mannoglucan from the bulbs of Lanzhou lily

An O-acetyl mannoglucan (BHP-1) from Lanzhou lily bulbs was structurally elucidated using partial acid hydrolysis, GC–MS, and 2D NMR techniques (COSY, NOESY, HSQC and HMBC) built on prior research, revealing a backbone of -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp- with the most potential side chains -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp-α-D-(1 → 4)-Glcp-α-D-(1 → Glcp- and -α-D-(1 → 4)-Glcp-β-D-(1 → 4)-Manp-α-D-(1 → Glcp-, attached to O-2 and O-3 of glucose and mannose residues, and featuring O-acetyl groups at O-2 or O-3 position of mannose. The terminal residue was α-D-(1 → Glcp. BHP-1 demonstrated anti-aging and hypoglycemic effects, as assessed by C. elegans model and glycolytic enzyme effect in vitro, respectively. The results showed that BHP-1 dose-dependently prolonged lifespan of C. elegans by 33 % at 4 mg/mL under normal conditions, with greater extensions under thermal and oxidative stress (50 % and 80 % increases, respectively, p < 0.05), which were attributed to enhanced antioxidant enzymes (SOD and CAT) and lowered MDA levels of C. elegans. Additionally, BHP-1 exhibited remarkable inhibition on α-glucosidase (93 %) and moderate inhibition on α-amylase (53 %) at 4 mg/mL, with competitive inhibition of α-glucosidase and mixed non-competitive inhibition of α-amylase, respectively. These potential effects might be linked to BHP-1's diverse sugar linkages, higher content of Glc, and certain O-acetyl contents.

Design, synthesis, biological evaluation, kinetic studies and molecular modeling of imidazo-isoxazole derivatives targeting both α-amylase and α-glucosidase inhibitors

Herein, a novel set of imidazo-isoxazole derivatives containing thiourea and urea scaffolds were synthesized, characterized (1H NMR, 13C NMR, and elemental analysis). These compounds were biologically evaluated for their α-amylase and α-glucosidase inhibitory activity, identifying 5f as the most active (IC50 26.67 ± 1.25 μM and 39.12 ± 1.83 μM against α-amylase α-glucosidase, respectively), better than the standard, acarbose. Enzymatic kinetic results showed that 5f and acarbose complete competitive type inhibitors. The structure-activity relationship (SAR) demonstrated that undergoing substitutions on R1 and R2 groups attached to the thiourea/urea moiety chains controlled the activity. Besides, in-silico ADMET study showed that almost title compounds exhibited satisfactory pharmacokinetic properties. In molecular docking study, the top performing compound (5f) exhibited higher binding energies (−5.501 and −6.414 kcal/mol, respectively) showing crucial interactions and that snuggly fit in their active site. To shed light on their mechanism of action, molecular dynamic (MD) simulations approach executed at 100 ns duration authenticated the high stability of 5f-1B2Y and 5f-3A4A complexes. The results of this investigation disclosed that compound 5f may serve as a potential lead, accomplished with in vivo studies, for the management of diabetes.

Synthesis, molecular modelling, and biological evaluation of novel quinoxaline derivatives for treating type II diabetes

Quinoxalines are benzopyrazine derivatives with significant therapeutic impact in the pharmaceutical industry. They proved to be useful against inflammation, bacterial, fungal, viral infection, diabetes and other applications. Very recently, in January 2024, the FDA approved new quinoxaline containing drug, erdafitinib for treatment of certain carcinomas. Despite the diverse biological activities exhibited by quinoxaline derivatives and the role of secretory phospholipase A2 (sPLA2) in diabetes-related complications, the potential of sPLA2-targeting quinoxaline-based inhibitors to effectively address these complications remains unexplored. Therefore, we designed novel sPLA2- and α-glucosidase-targeting quinoxaline-based heterocyclic inhibitors to regulate elevated post-prandial blood glucose linked to patients with diabetes-related cardiovascular complications. Compounds 5a–d and 6a–d were synthesised by condensing quinoxaline hydrazides with various aryl sulphonyl chlorides. Biological screening revealed compound 6a as a potent sPLA2 inhibitor (IC50 = 0.0475 µM), whereas compound 6c most effectively inhibited α-glucosidase (IC50 = 0.0953 µM), outperforming the positive control acarbose. Moreover, compound 6a was the best inhibitor for both enzymes. Molecular docking revealed pharmacophoric features, highlighting the importance of a sulfonohydrazide moiety in the structural design of these compounds, leading to the development of potent sPLA2 and α-glucosidase inhibitors. Collectively, our findings helped identify promising candidates for developing novel therapeutic agents for treating diabetes mellitus.

Benzothiazole derivatives as effective α-glucosidase inhibitors: an insight study of structure-activity relationships and molecular targets

Benzothiazole derivatives as effective α-glucosidase inhibitors: an insight study of structure-activity relationships and molecular targets

Phytochemical composition of &lt;i&gt;Eriobotrya japonica&lt;/i&gt; (Rosaceae) leaves extracts from central Veracruz, Mexico, and its effect on α-glucosidase enzyme inhibition

Background: Eriobotrya japonica is economically significant as an ornamental tree, and its leaves have medicinal properties. Question: What are the main chemical components of loquat leaves grown in a population of Central Veracruz Mexico? and does the methanolic extract have potential antidiabetic properties through α-glucosidase inhibition? Species study: Eriobotrya japonica (Thunb.) Lindl. (Rosaceae) Study site and date: Xalapa, Veracruz, Mexico, 2021-2022. Methods: Total carbon (C) and nitrogen (N) content, phosphorus (P), sodium (Na), potassium (K), calcium (Ca), and magnesium (Mg) were determined in leaves powder. Leaf methanol extract of E. japonica was tested for α-glucosidase inhibition. Also, different groups of secondary metabolites were detected by the phenolics/volatile-targeted metabolomic analysis. Results: The leaves of E. japonica are rich in C and minerals such as Na, K, Ca, and Mg, and contain high levels of flavonoids, and procyanidin B2. The leaf methanol extract (LME) effectively inhibited α-glucosidase activity (86.05 ± 0.73 %) in vitro. In addition, a leaf petroleum ether extract (LPE) contains mainly phytol, palmitic acid, linoleic acid, stearic acid, and phytol acetate. Conclusions: The leaf methanolic extract exhibited antidiabetic potential due to its potent α-glucosidase inhibition, and the presence of diverse phenolic compounds, including flavonoids and their glycoside derivatives, and some fatty acids further supports the traditional use of E. japonica as an herbal medicine with antidiabetic properties.

The use of Oral Anti-Diabetic Medications in Diabetes Mellitus type 1: An Educational Article and Expert Opinion

Diabetes mellitus type 1 is lifelong condition resulting from failure of production of insulin because of the loss of pancreatic islet beta-cells because of autoimmune damage. Patients with this type of diabetes need lifelong treatment with insulin to remain alive. Poor diabetic control which predisposes to a variety of complications is not uncommon in patients treated with insulin alone. Therefore, the use of medications that can possibly enhance the therapeutic effect of insulin and reduce the risk of diabetic complications has been considered. Oral anti-diabetics including acarbose, an inhibitor of intestinal α-glucosidase, metformin, a biguanide, sulfonylureas including glipizide, and sitagliptin, an inhibitor of dipeptidyl peptidase 4 (DPP-4) are primarily used for the treatment of non-insulin dependent diabetes (Type 2). The aim of this paper is to provide an overview of the use of oral anti-diabetics in the treatment of insulin dependent diabetes (Type 1). Expert opinion: The current evidence-based expert opinion recommends the judicious use of oral anti-diabetics especially acarbose and metformin in the treatment of unsatisfactorily controlled insulin dependent diabetes type 1. These medications can help in improving diabetic control through reducing glucose levels after meals, and can contribute to lowering the levels of glycosylated hemoglobin (HbA1c). The use of these oral anti-diabetics can also help in reducing insulin requirement.

Correction: Cassia siamea Role in Diabetes Management: Insights from In vitro and In silico Investigations on α-Glucosidase and α-Amylase Inhibition

Correction: Cassia siamea Role in Diabetes Management: Insights from In vitro and In silico Investigations on α-Glucosidase and α-Amylase Inhibition

Antioxidant and Biological Activity of Mexican Madroño Fruit (Arbutus arizonica).

The fruit of the Mexican madroño (Arbutus arizonica) has been consumed since pre-Columbian times by North American tribes and native groups in Mexico. Despite this, reports on its chemical composition and biological activity are limited. This work aims to determine the antioxidant, antiproliferative, and digestive enzyme inhibition activities of the methanol amberlite-retained extract of Mexican madroño. Results showed that madroño fruit is rich in antioxidants: DPPH (EC50 = 0.89 ± 0.03 mg/mL), TEAC (1078 ± 4.9 μM/g), and hemolysis inhibition (IC50 = 358.07 μg/mL), with high phenolic and flavonoid content at 15.92 ± 3.2 mg GAE/g and 4.33 ± 0.3 mg CA/g, respectively. Using analytical chromatography, gallic acid, vanillic acid, chlorogenic acid, ferulic acid, quercetin, and rutin were quantified. The extract also showed α-glucosidase inhibition (IC50 = 3.1 ± 0.17 mg/mL), but no inhibition against α-amylase and lipase (>5 mg/mL), while showing antiproliferative activity against HeLa, HT-29, and MCF-7 cancer cell lines. These results point towards an interesting potential for the fruit of the A. arizonica as chemopreventive and hold potential for elaborating functional foods.

Natural α-glucosidase inhibitors from Aquilaria sinensis leaf-tea: Targeted bio-affinity screening, identification, and inhibition mechanism

Aquilaria sinensis leaves have long been consumed as a popular replacement tea for lowering postprandial blood glucose levels, but their specific functional components remain unclear. In this study, Aquilaria sinensis leaf-tea 70 % ethanol extract (ALTE) exhibited excellent anti-α-glucosidase activity (IC50 = 6.93 ± 1.91 μg/mL) and promoted glucose consumption ability in 3 T3-L1 preadipocyte cells. Subsequently phenolic compositions of ALTE were identified for the first time. After that, five potential α-glucosidase inhibitors (α-GIs) including cynaroside-3,5-diglucose, malvidin 3-glucose, epicatechin, epigallocatechin gallate, and dihydromyricetin in ALTE were screened using a targeted bio-affinity ultrafiltration-HPLC/MS method. Moreover, these five α-GIs all showed good anti-α-glucosidase effects and glucose consumption-promoting ability. Furthermore, the binding properties and inhibition mechanisms of five α-GIs to α-glucosidase were further analyzed via enzyme inhibition kinetics, molecular docking, and molecular dynamics simulation. This study confirms that Aquilaria sinensis leaf-tea is effective in preventing post-hyperglycemia in vitro models, suggesting potential for future research in human trials.

Evaluation of α-glucosidase inhibitor activity and bioactive compounds in purple wheat flour yogurts

Nowadays, the food industry attaches more importance to studies on using purple components in food formulations due to their bioactive properties. This study evaluated the phenolic compound content, antioxidant activity, physicochemical properties, sensory properties, and α-glucosidase activities in yogurt enriched with purple wheat flour. Yogurts were produced using varying concentrations of purple wheat flour labeled as sample A (1.5 %), sample B (3 %), and sample C (4.5 %). It was observed that incorporating purple wheat flour led to a decrease in pH and an increase in L*, a*, and b* values, as well as the acidity and viscosity of the yogurts. Sample C contained the highest phenolic content (37.6 mg GAE/100 g dry matter) on day 14, along with the highest flavonoid content (14.59 mg CE/100 g) on day 21 when than control yogurt. In addition, sample C had the highest α-glucosidase activity (38.35 %) on day 14 and anthocyanin content (13.55 g/100 g) on day 21. As a result, C yogurt can be consumed as a diabetic product with antidiabetic and antihypertensive properties by reaching optimal α-glycosidase inhibition activity. Furthermore, yogurts containing purple wheat flour received higher sensory scores from panelists.

Antidiabetic and Antioxidant Activities of Indian Bay Leaf (Cinnamomum tamala (Buch.-Ham.) T. Nees & Eberm.) Essential Oils Collected from Meghalaya.

The current work investigates the chemodiversity, in vitro antioxidant, α-amylase and α-glucosidase inhibitory potential of Cinnamomum tamala (CT) leaf essential oil (EO) collected from different localities of East Khasi Hills District of Meghalaya, India. Gas chromatography-mass spectrometry (GC-MS) analysis of all the extracted leaf essential oils facilitated the identification of several compounds in a variable range along with eugenol as the major component (74.79-95.12 %). CT8 exhibited the highest antioxidant activity (IC50=11.23±0.27 μg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and IC50=21.54±0.37 μg/mL for 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) among all EO evaluated. The results showed that the ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) values for CT8 were 83.26±1.92 μM trolox/g oil and 70.29±1.90 ascorbic acid equivalents (AAE)/g of oil. α-amylase and α-glucosidase inhibition were highest in sample CT8 with IC50 values of 3.62±0.42 μg/mL and 16.29±0.32 μg/mL respectively. Caryophyllene, cyclohexene, 1, 5, 5-trimethyl-6-(2-propenylidene), germacrene D and eugenol showed strong binding potential toward α-amylase and α-glucosidase. It concluded that the chemodiversity and antidiabetic potential of C. tamla oil from Khasi Hills have never been studied. It can be taken as a dietary supplement as an antioxidant and antidiabetic to control blood glucose.

Synthesis of novel thiazole derivatives containing 3-methylthiophene carbaldehyde as potent anti α-glucosidase agents: In vitro evaluation, molecular docking, dynamics, MM-GBSA, and DFT studies

Thiazole derivatives bearing thiophene carbaldehyde have been successfully prepared by refluxing 3-methylthiophene carbaldehyde with thiosemicarbazide in absolute ethanol followed by treating the obtained product with different phenacyl bromide to get thiazole products in better yields. These derivatives were confirmed using 1H-, 13C NMR, and EI-MS spectrometry techniques and finally subjected for their α-glucosidase inhibitory potential. Two compounds in the series including 2 g (IC50 = 9.00 ± 0.57 µM) and 2b (IC50 = 13.50 ± 0.20 µM) were found as the most potent α-glucosidase inhibitors better than the standard acarbose. Furthermore, the remaining five compounds attributed significantly to less activity. The studied molecules were calculated on the 6–31++g(d,p) basis set at B3LYP, HF, M062X levels with the help of the Gaussian package program, and their chemical activities were compared. Following that, the molecules' interactions with different α-glucosidase proteins (PDB IDs: 1R47 and 1UAS) were investigated, and their activities were contrasted. The binding free energy of the molecule with the best docking score is computed using MM/GBSA techniques. The comparative molecular dynamics simulations of the 2g-1UAS and 2g-1R47 complexes highlight the intricate balance of forces that govern biomolecular interactions. The findings suggest that while the 2g-1UAS complex forms more stable interactions, as indicated by lower RMSD values, the 2g-1R47 complex maintains its structural integrity through strong hydrogen bonds. Overall, the equilibrium conformations achieved by both complexes suggest they are well-suited for their roles in physiological environments.

Enrichment of deoxynojirimycin in mulberry using cation exchange resin: Adsorption/desorption characteristics and process optimization

Deoxynojirimycin (DNJ) is an α-glucosidase inhibitor with high food values. However, the complex and costly enrichment processes have greatly prevented its application. Herein, this study aimed to propose a simple and efficient enrichment process for DNJ from Morus alba L. extracts using cation exchange resins. The LSI and D113 resins were chosen due to their excellent adsorption and desorption properties. The adsorption characteristics agreed with the pseudo-first-order kinetic model and the Langmuir isotherm model. This adsorption was chemisorption, spontaneous, endothermic and entropy-driven. Furthermore, the concentration and pH of the extracts, desorption solvent, breakthrough and elution curves, sample loading and elution rate were investigated to optimize the enrichment process by resin column chromatography. The results also showed that the purity of DNJ was improved to 44.00 % with a total recovery of 78.21 % using the LSI-D113 combination strategy. This research demonstrated the industrial feasibility of DNJ enrichment using cation exchange resins.

Novel α-glucosidase Inhibitors Designed as Type 2 Diabetes Drugs by QSAR, Molecular Docking and Molecular Dynamics Simulation Methods.

Diabetes mellitus is a globally prevalent disease of significant concern. Alpha-glucosidase has emerged as a prominent target for the treatment of type 2 diabetes. In this study, 39 α-glucosidase inhibitors (AGIs) of tetrahydrobenzo[b]thiophene-2-ylurea derivatives to establish a stable and valid Topomer CoMFA model, with a cross-validation coefficient (q²) of 0.766 and a non-cross-validation coefficient (r²) of 0.960. Subsequently, the ZINC15 database was used to screen the fragments, based on which 13 novel inhibitor molecules with theoretically potentially high activity were designed. Molecular docking and molecular dynamics simulations to understand the binding status of the inhibitor molecules to the target proteins showed that amino acids ASP215, GLN279 and ARG442 may form hydrogen bonds with the ligands and therefore enhance the inhibitory effect of the small molecules. Additionally, MM/PBSA calculations suggest that the newly designed molecules demonstrate more stable binding modes, and these newly designed molecules showed good ADMET properties with potential as AGIs. The findings would provide valuable guidance and a theoretical foundation for the design and development of novel AGIs.

Identification of natural curcumins as potential dual inhibitors of PTP1B and α-glucosidase through experimental and computational study

Curcuma longa is a rich source of curcumin (1) and its major analogs, demethoxycurcumin (2), and bisdemethoxycurcumin (3), among the Curcuma species. In this study, curcumins (1–3) were purified from C. longa, and their inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase enzymes were assayed. These compounds potential inhibited PTP1B and α-glucosidase activities with IC50 values ranging from 37.8 to 72.6 μM, and 78.2–90.6 μM, respectively. In addition, density functional theory (DFT) accompanied by molecular docking (MD) were employed to analyze the ligand stability and the interaction of curcumins 1–3 with PTP1B and glucoside hydrolase proteins. The assay-based results and MD data obtained showed a high correlation, suggesting that the deterioration of enzyme activity caused by the distortion of the structural conformation of PTP1B and glucoside hydrolase may be related to the arrangement of amino acids in the protein structure. Our findings reveal the significant role of methoxylation in the variation of inhibitory effects of these curcumins against PTP1B and α-glucosidase. These in vitro and in silico activities of curcumins (1–3) against PTP1B and glucoside hydrolase have been examined and reported for the first time.

UHPLC-Q-TOF-MS/MS identification of metabolites in cereal beverage ‘Borde’ and its anti-obesity efficacy in Caenorhabditis elegans model

This research explores the remarkable impact of fermented cereals such as sorghum, maize, and wheat with Pediococcus acidilactici WS07, a strain isolated from Ethiopia's traditional borde beverage. The fermented cereal extracts were thoroughly evaluated for antioxidant activity, inhibition of pancreatic lipase and α-glucosidase, metabolite identification through UHPLC-Q-TOF-MS/MS, and in vivo efficacy using the C. elegans model. The results revealed significant enhancements in the bioactive compounds of fermented cereals, demonstrating promising directions for obesity prevention strategies. Notably, the fermented sorghum extracts improved lipase (88.23 %) and α-glucosidase (85.62 %) inhibitory activities compared to its unfermented counterparts. The antioxidant properties of all fermented samples were confirmed through improved DPPH (67.77–71.86 %) and ABTS (59.91–65.49 %) scavenging activities. Fermentation also led to a notable increase in polyphenols and flavonoids, with detailed metabolite analysis revealing a dynamic shift in the composition of these bioactive compounds. Additionally, C. elegans indicates that fermented extracts extend lifespan, reduce lipid accumulation, and lower triglycerides, highlighting their potential as functional foods for health enhancement and obesity management. This study not only underscores the efficacy of P. acidilactici WS07 fermentation in transforming cereals into nutrient-rich functional foods but also provides insight into how microbial fermentation can unlock the health-promoting potential of traditional diets.