Potent Α-glucosidase Inhibitors Research Articles

Chemical Composition, Anti-α-Glucosidase Activity, and Molecular Modelling Studies of Cleistocalyx operculatus Essential Oil

In this study, chemical components, α-glucosidase inhibitory activities, and molecular modelling studies of the essential oil extracted from the Cleistocalyx operculatus leaves were investigated. In total, thirty compounds were identified using GC/MS, representing 98.3% of the oil. Of these, the two most dominant constituents of the essential oil were determined as (Z)-β-ocimene (30.4%) and allo-ocimene (31.6%). The α-glucosidase inhibitory experiments indicated that the essential oil exhibited potent α-glucosidase inhibitory activities, with IC50 values of 61.82 ± 3.91 µg/mL. For further investigation into inhibitory mechanisms, molecular docking simulations were performed to investigate structural interactions between two dominant constituents and the α-glucosidase protein. The simulation revealed that allo-ocimene (31.6%) and (Z)-β-ocimene (30.4%) have protein binding affinities of −5.358 and −5.330 kcal/mol, respectively. Moreover, molecular dynamic simulation indicated that the complexes of two compounds and the target protein were stable over 100 ns. Overall, these findings suggest that the essential oil of C. operculatus leaves could be a natural source of potential α-glucosidase inhibitors.

Phytochemical analysis, antioxidant, α-glucosidase inhibitory activity, and toxicity evaluation of Orthosiphon stamineus leaf extract

Ocimum aristatum, commonly known as O. stamineus, has been widely studied for its potential as an herbal medicine candidate. This research aims to compare the efficacy of water and 100% ethanolic extracts of O. stamineus as α-glucosidase inhibitors and antioxidants, as well as toxicity against zebrafish embryos. Based on the study findings, water extract of O. stamineus leaves exhibited superior inhibition activity against α-glucosidase, ABTS, and DPPH, with IC50 values of approximately 43.623 ± 0.039 µg/mL, 27.556 ± 0.125 µg/mL, and 95.047 ± 1.587 µg/mL, respectively. The major active compounds identified in the extract include fatty acid groups and their derivates such as linoleic acid, α-eleostearic acid, stearic acid, oleanolic acid, and corchorifatty acid F. Phenolic groups such as caffeic acid, rosmarinic acid, 3,4-Dihydroxybenzaldehyde, norfenefrine, caftaric acid, and 2-hydroxyphenylalanine and flavonoids and their derivates including 5,7-Dihydroxychromone, 5,7-Dihydroxy-2,6-dimethyl-4H-chromen-4-one, eupatorin, and others were also identified in the extract. Carboxylic acid groups and triterpenoids such as azelaic acid and asiatic acid were also present. This study found that the water extract of O. stamineus is non-toxic to zebrafish embryos and does not affect the development of zebrafish larvae at concentrations lower than 500 µg/mL. These findings highlight the potential of the water extract of O. stamineus as a valuable herbal medicine candidate, particularly for its potent α-glucosidase inhibition and antioxidant properties, and affirm its safety in zebrafish embryos at tested concentrations.

In Silico Analysis of Phenolic Compounds from Ceriops decandra Griff. Leaves and Molecular Interaction as Anti Diabetes

α-amylase and α-glucosidase in the gastrointestinal tract have an important role in the hydrolysis α-1,4 and α-1,6 glycosidic chain of starch, respectively. Inhibition of both enzyme activities becomes one of the strategies to control diabetes. However, commercial drugs such as antidiabetics have adverse effects such as gastrointestinal problems. Therefore, exploring functional food, especially from marine natural products as antidiabetic agents, is potential. In particular, Ceriops sp. was reported to contain bioactive compounds with antidiabetic properties, but its mechanism to treat diabetes has not been proved. The potency of phenolic compounds of C. decandra leaves as α-amylase and α-glucosidase inhibitors were examined in this research by implementing the molecular docking analysis in silico. Three steps of analysis were carried out in this study, including extraction from C. decandra leaves with different polarity solvents, identification of phenolic compounds using LC-HRMS, and molecular docking analysis of phenolic compounds identified from C. decandra leaves. This study revealed that quercetin, rutin, epicatechin, isorhamnetin, caffeic acid, and ferulic acid were identified from C. decandra leaves. According to the drug-likeness and toxicity analysis, the presented compounds in C. decandra leaves had high potential pharmacological properties. Furthermore, molecular interaction analysis exhibited phenolic compounds extracted with ethyl acetate, such as quercetin and epicatechin, and with methanolic extracts, such as quercetin, rutin, epicatechin, and isorhamnetin, were more effective as α-amylase and α-glucosidase inhibitors than from caffeic acid and ferulic acid. Among the phenolic compounds of C. decandra leaves, rutin and quercetin were predicted to be the potential α-glucosidase inhibitors.

Synthesis, density functional theory and kinetic studies of aminopyridine based α-glucosidase inhibitors.

Aims: The current study aimed to develop new thiourea derivatives as potential α-glucosidase inhibitors for the management of hyperglycemia in patients of Type 2 diabetes, with a focus on identifying safer and more effective antidiabetic agents. Materials & methods: New thiourea derivatives (1-16) were synthesized through single-step chemical transformation and evaluated for in vitro α-glucosidase inhibition. Kinetic studies identified the mode of inhibition, free energy and type of interactions were analyzed through density functional theory and molecular docking. Results & conclusion: Compound 5 was identified as the most potent, noncompetitiveand noncytotoxic inhibitor of α-glucosidase enzyme with half-maximal inhibitory concentration of 24.62±0.94μM. Computational studies reinforce experimental results, demonstrating significant enzyme interactions via hydrophobic and π-π stacking forces.

Comparison of inhibitory activities of 50 Salvia species against α-Glucosidase.

Type 2 diabetes is a common metabolic disease affecting millions of people worldwide. α-Glucosidase inhibitors can be used as one of the therapeutic approaches to decrease the postprandial glucose levels through the inhibition of carbohydrate hydrolysis. Medicinal plants are one of the main sources of α-glucosidase's natural inhibitors. In this study, we report the inhibitory effects of 50 different accessions of 32 Salvia species against α-glucosidase. To estimate the relative potency of the crude extracts, the inhibitory activities of the 80% methanol of the plants extracts were determined in three different concentrations (1000, 500 and 250µg/ml) and compared to that of acarbose as the positive control. S. multicaulis, S. santolinifolia, S. dracocephaloides, and S. eremophila were stronger inhibitors than acarbose (p < 0.05) with IC50 values in the range of 26.23- 92.35µg/mL. According to the LC-PDA-ESIMS and NMR analysis of crude extracts of the studied Salvia species, 8 phytochemicals including luteolin-7-O-glucoside (1) luteolin-7-O-glucuronide (2), apigenin-7-O-glucoside (3), apigenin-7-O-glucuronide (4), Hispidulin-7-O-glucuronide (5), hispidulin-7-O-glucoside (6), rosmarinic acid (7), carnosol (8) and carnosic acid (9) were identified as the most common α-glucosidase inhibitors. The above compounds constituted the major compounds in the active Salvia species in the range of 1.5-95.0%. Among them rosmarinic acid (39-95%) was detected in almost all potent α -glucosidase inhibitor species. Therefore, it can be considered as a biochemical marker in the antidiabetic Salvia species in addition to the other minor compounds. Considering the high α-glucosidase inhibitory potential of the four- out of fifty Salvia species, they are suggested for further in vivo antidiabetic tests as potential medicinal plants.

Synthesis and biological evaluation of chromone-thiazolidine-2,4-dione derivatives as potential α-glucosidase inhibitors

A series of chromone-thiazolidine-2,4-dione derivatives (e1 ∼ 28) were synthesized and screened for their α-glucosidase inhibitory. All synthetic derivatives presented excellent α-glucosidase inhibitory with IC50 values ranging from 2.40 ± 0.11 to 5.66 ± 0.15 μM, comparing to positive control acarbose (IC50 value: 640.57 ± 5.13 μM). Among them, compound e28 displayed the strongest α-glucosidase inhibitory (IC50 value: 2.40 ± 0.11), ∼267 times stronger than positive control acarbose. Kinetic studies revealed that compound e28 was a reversible non-competitive inhibitor. CD spectra and 3D fluorescence spectra results explained that compound e28 changed the conformational changes of α-glucosidase. Molecular docking simulated the binding between compound e28 and α-glucosidase. In vitro cytotoxicity assay ascertained the good security of e28.

Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach.

A new series of thiazole derivatives (4a-p) incorporating imidazopyridine moiety was synthesized and assessed for their in vitro potential α-glucosidase potency using acarbose as a reference drug. The obtained results suggested that compounds 4a (docking score = -13.45), 4g (docking score = -12.87), 4o (docking score = -12.15), and 4p (docking score = -11.25) remarkably showed superior activity against the targeted α-glucosidase enzyme, with IC50 values of 5.57 ± 3.45, 8.85 ± 2.18, 7.16 ± 1.40, and 10.48 ± 2.20, respectively. Upon further investigation of the binding mode of the interactions by the most active scaffolds with the α-glucosidase active sites, the docking analysis was accomplished in order to explore the active cavity of the α-glucosidase enzyme. The interpretation of the results showed clearly that scaffolds 4a and 4o emerged as the most potent α-glucosidase inhibitors, with promising excellent binding interactions with the active site of the α-glucosidase enzyme. Furthermore, utilizing a variety of spectroscopic methods, such as 1H-NMR, 13C-NMR, and HREI-MS, the precise structures of the synthesized scaffolds were determined.

Identification of 1,3,4-oxadiazolyl-containing β-carboline derivatives as novel α-glucosidase inhibitors with antidiabetic activity

In this study, we designed and synthesized a novel class of 1,3,4-oxadiazolyl-containing β-carboline derivatives, i.e., compounds f1∼f35 as potential α-glucosidase inhibitors. All the synthesized compounds possessed outstanding α-glucosidase inhibitory activity with the IC50 values in the range of 3.07–15.49 μM, representing that they are 36∼183-fold more active than a positive control, acarbose (IC50 = 564.28 μM). Among them, compound f26 exhibited the highest α-glucosidase inhibitory activity (IC50 = 3.07 μM) and was demonstrated to function as a reversible and noncompetitive inhibitor. Mechanistic studies by means of 3D fluorescence spectra, CD spectra and molecular docking suggested that complexation of compound f26 with α-glucosidase through hydrogen bonds and hydrophobic interactions, led to changes in the conformation and secondary strictures of α-glucosidase and further the inhibition of the enzymatic activity. In vivo results showed that oral administration of compound f26 (50 mg/kg/day) could obviously reduce the levels of fasting blood glucose and improve glucose tolerance and dyslipidemia in diabetic mice. The present findings suggest that compound f26 is exploitable as a potential lead compound for the development of new α-glucosidase inhibitors with antidiabetic activity.

Design, synthesis, biological evaluation, and docking study of new triazole-phenylacetamide derivatives as α-glucosidase inhibitors

To discover potent α-glucosidase inhibitors, a class of novel triazole-phenylacetamide derivatives (5a-5p) were designed, prepared, and tested for their α-glucosidase inhibitory effects. All tested compounds (5a-5p) displayed a strong α-glucosidase inhibitory activity (IC50 = 6.69 ± 0.18–113.65 ± 2.94 μM) in comparison with the positive control acarbose (IC50 = 723.06 ± 11.26 μM). Thereinto, 5g (IC50 = 6.69 ± 0.18 μM) showed the best anti-α-glucosidase activity and behaved as a mixed-type inhibitor with the value of Ki and Kis to be 1.65 μM and 4.54 μM, respectively. Besides, fluorescence quenching experiment, three-dimensional fluorescence spectra assay, circular dichroism analysis, and molecular docking studies indicated that 5g may inhibit α-glucosidase activity by binding with its active site as well as changing the secondary structure of α-glucosidase. Combined with the inhibition effect on the rise of postprandial blood glucose level and low cytotoxicity of 5g, it could be concluded that these title compounds may play a role as lead compounds to develop novel α-glucosidase inhibitors.

Spectral characterization and binding dynamics of bioactive compounds from Chlorella minutissima against α-glucosidase: An in vitro and in silico approach

Management of type-II diabetes through regulating the activity of α-glucosidase is a promising therapeutic approach. Here, bioassay-guided isolation of algal secondary metabolites (ASM) from microalgae (Chlorella minutissima) inhibiting α-glucosidase was explored. In this study, the purified column fractions (SIV-P2) of C. minutissima acetone extract obtained from flash chromatography exhibited α-glucosidase inhibition potential with the IC50 value of 1.61 mg mL−1, and the active fractions were dominated by terpenoids and alkaloids. Further, molecular dynamics simulations revealed that Lucidine B, an alkaloid compound possesses the least binding energy (BE) of −318 KJ mol−1 when compared to the standard drug acarbose (−216.781 KJ mol−1). Lucidine B formed a hydrogen bond with Glu408 which possibly induced cleft closure and prevented the substrate entry to the active site (non-competitive inhibition). The present study unveils that ASM could be exploited as a potential inhibitor of α-glucosidase and may be used for the alleviation of type-II diabetes.

Synthesis of novel coumarin-hydrazone hybrids as α-glucosidase inhibitors and their molecular docking studies.

Diabetes mellitus is a metabolic disorder and more than 90% of diabetic patients suffer from type-2 diabetes, which is characterized by hyperglycemia. α-Glucosidase inhibition has become an appropriate approach to tackle high blood glucose levels. The current study was focused on synthesizing coumarin-hydrazone hybrids (7a-i) by using facile chemical reactions. The synthesized compounds were characterized by using 1H-NMR, 13C-NMR, and IR. To evaluate their anti-diabetic capability, all of the conjugates were screened for in vitro α-glucosidase inhibitory activity to reveal their therapeutic importance. All of the compounds (except 7b) demonstrated significant enzyme inhibitory potential with IC50 values ranging between 2.39-57.52 μM, as compared to the standard inhibitor, acarbose (IC50 = 873.34 ± 1.67 μM). Among them, compound 7c is the most potent α-glucosidase inhibitor (IC50 = 2.39 ± 0.05 μM). Additionally, molecular docking was employed to scrutinize the binding pattern of active compounds within the α-glucosidase binding site. The in silico analysis reflects that hydrazone moiety is an essential pharmacophore for the binding of compounds with the active site residues of the enzyme. This study demonstrates that compounds 7c and 7f deserve further molecular optimization for potential application in diabetic management.

Utilizing bio-affinity ultrafiltration combined with UHPLC Q-Exactive Plus Orbitrap HRMS to detect potential α-glucosidase inhibitors in Oxalis corniculate L.

Oxalis corniculate L. (O. corniculate) was used to treat diabetes in Chinese folk as a popular tea drink. In this work, 31 compounds from O. corniculate were screened and identified as potential α-Glucosidase inhibitors (α-GIs). Among them, 6 compounds displayed stronger inhibitory activity than acarbose (IC50 = 212.9 ± 5.98 μg/mL). Especially, the most effective compounds quercetin (Qu, IC50 = 4.70 ± 0.40 μg/mL) and luteolin (Lu, IC50 = 15.72 ± 0.75 μg/mL) inhibited α-Glu in competitive and mixed manners, respectively. Moreover, fluorescence quenching, circular dichroism (CD), and molecular docking study revealed that they can arouse the changes in the secondary structure and hydrophobic micro-environment of the enzyme mainly through a hydrophobic binding. Furthermore, it was observed that oral administration of Qu (20 mg/kg) can significantly reduce postprandial blood glucose (PBG) levels in mice vs. the control group. To sum up, the above research confirmed that O. corniculate could prevent and treat postprandial hyperglycemia as a good tea drink, and the plant was an excellent source to obtain natural α-GIs.

Phytoligands analysis of aqueous seed extract of Momordica charantia Linn. via GC-MS for its antidiabetic activity

In India, Momordica charantia Linn. is utilized in juices, health supplements and colouring agents. The aim of the current study is to analyze phytoligands by utilizing gas chromatography mass spectroscopy of aqueous seed extract of Momordica charantia Linn (MCA). The MCA was prepared by macerating the powdered seeds for 72 hrs followed by filtration and lyophilization followed by an in vitro α-glucosidase inhibitory activity. MCA was the potent inhibitor of α-glucosidase with IC50 value 73.75± 0.05 μg/ml. The analysis through GC-MS investigated 60 phytoconstituents which were validated using Schrodinger suite version 2020-3 against α-glucosidase (PDB ID- 5NN5). As per docking results, the existing phytochemicals azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl)-, alpha-l-rhamnopyranose, piperidine, 3-methyl-, 1,4-Dioxane-2,5-dione,3,6-dimethyl and citronellol epoxide (R or S) from MCA, got the highest d-score of -7.230, -5.918, -5.643, -5.312 and -5.185 kcal/mol and could be promising antidiabetic drug candidates.

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling.

Hyperglycemia, as a hallmark of the metabolic malady diabetes mellitus, has been an overwhelming healthcare burden owing to its high rates of comorbidity and mortality, as well as prospective complications affecting different body organs. Available therapeutic agents, with α-glucosidase inhibitors as one of their cornerstone arsenal, control stages of broad glycemia while showing definitive characteristics related to their low clinical efficiency and off-target complications. This has propelled the academia and industrial section into discovering novel and safer candidates. Herein, we provided a thorough computational exploration of identifying candidates from the marine-derived Aspergillus terreus isolates. Combined structural- and ligand-based approaches using a chemical library of 275 metabolites were adopted for pinpointing promising α-glucosidase inhibitors, as well as providing guiding insights for further lead optimization and development. Structure-based virtual screening through escalating precision molecular docking protocol at the α-glucosidase canonical pocket identified 11 promising top-docked hits, with several being superior to the market drug reference, acarbose. Comprehensive ligand-based investigations of these hits' pharmacokinetics ADME profiles, physiochemical characterizations, and obedience to the gold standard Lipinski's rule of five, as well as toxicity and mutagenicity profiling, proceeded. Under explicit conditions, a molecular dynamics simulation identified the top-stable metabolites: butyrolactone VI (SK-44), aspulvinone E (SK-55), butyrolactone I 4''''-sulfate (SK-72), and terrelumamide B (SK-173). They depicted the highest free binding energies and steadiest thermodynamic behavior. Moreover, great structural insights have been revealed, including the advent of an aromatic scaffold-based interaction for ligand-target complex stability. The significance of introducing balanced hydrophobic/polar moieties, like triazole and other bioisosteres of carboxylic acid, has been highlighted across docking, ADME/Tox profiling, and molecular dynamics studies for maximizing binding interactions while assuring safety and optimal pharmacokinetics for targeting the intestinal-localized α-glucosidase enzyme. Overall, this study provided valuable starting points for developing new α-glucosidase inhibitors based on nature-derived unique scaffolds, as well as guidance for prospective lead optimization and development within future pre-clinical and clinical investigations.

Triazolothiadiazoles and triazolothiadiazines as potent α-glucosidase inhibitors: Mechanistic insights from kinetics studies, molecular docking and dynamics simulations

Diabetes mellitus has been considered as a serious health problem worldwide due its high prevalence rate and associated complications. In this context, the current research work aims at exploring new structural leads for the treatment of a major metabolic disorder, diabetes mellitus type 2. The outcomes of our prior studies on a diverse set of triazolothiadiazole and triazolothiadiazine derivatives and their therapeutic potential, encouraged us to explore their anti-diabetic competency by targeting the key carbohydrate catabolic enzyme, α-glucosidase. Therefore, all these analogues were examined to reveal their contribution towards this severe metabolic issue. Interestingly, all the tested compounds (2a-2l and 3a-3p) exhibited several times more potent α-glucosidase inhibitory activities (IC50 in the range of 2.44–219.93 μM) as compared to marketed drug, acarbose (IC50 = 873.34 ± 1.67 μM). Furthermore, their mechanism of action was investigated through in vitro kinetics studies which revealed compounds 3a, 3d, 3o, and 2k as competitive inhibitors, and 3f as a mixed type inhibitor of α-glucosidase. In addition, in silico molecular docking and molecular dynamics simulations were applied to observe the mode of interaction of the active hits within the binding pocket of α-glucosidase. Both docking and simulation results favored our in vitro mechanistic analysis.

Antioxidant, α-amylase and α-glucosidase Inhibitory Activities of Aqueous and Methanolic Extracts From Athamanta sicula L.

Introduction: Oxidative stress plays a major role in developing diabetes complications; therefore, it is possible to use natural antioxidants as therapeutic agents for diabetes. Aims: This study aimed to find an important source of phenolics from Athamanta sicula L. (A. sicula) and confirm that this plant could be a significant source of medically important natural compounds by confirming its antioxidant, α-amylase and α-glucosidase inhibitory potential. Methods: Antioxidant property was performed using 2,2′-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, metal chelating, and cupric reducing antioxidant capacity methods. The α-amylase and α- glucosidase inhibitory activities were investigated using an in vitro model. Moreover, polyphenols and flavonoid contents of the tested extracts were carried out. Results: The methanolic extract exhibited the highest phenolic and flavonoid content compared to the aqueous extract. However, aqueous extract possessed the strongest antioxidant activity (DPPH scavenging, metal chelating, and Cupric ion reducing antioxidant capacities), α-amylase and α-glucosidase inhibitory effects. No correlation between phenolic content and antioxidant and enzyme inhibitory activities of A. sicula L. extracts was observed. Conclusion: The results showed that this plant could be a significant source of medically important natural compounds.

Antidiabetic potential of Amomum dealbatum Roxb. flower and isolation of three bioactive compounds with molecular docking and in vivo study

Amomum dealbatum Roxb. parts have been traditionally used as remedies for joint pain, diabetes, muscular rheumatism, antiseptic, and abscesses in Arunachal Pradesh, Assam, and Tripura. Ethyl acetate sub-fraction E3 had significantly inhibited the α-glucosidase (IC50 5.385 μg/mL). The molecular docking revealed quercetin-3-O-galactoside to be the most potent α-glucosidase inhibitor (binding energy −43.214 kcal/mol). Using the QSAR model, the pIC50 values of myricetin, gallic acid, quercetin-3-O-galactoside, and acarbose were predicted to be 5.65235, 4.39858, 5.65235, and 6.03058, respectively. For the first time, quercetin-3-O-galactoside, myricetin, and gallic acid have been isolated from the flowers of A. dealbatum (ADF). E3 decreased blood glucose level to a near-normal concentration (100.60 ± 2.94 mg/dL) in comparison to diabetic control rats (575.20 ± 24.80 mg/dL). The results have strongly suggested the potential of ADF in treating diabetes. This lesser-known plant has the potential to uncover its full medicinal properties through further in-depth research.

ANTIOXIDANT, ENZYME INHIBITORY, AND CYTOTOXIC ACTIVITY SCREENING OF MYRTUS COMMUNIS L.

Objective: The present study aimed to evaluate the biological activities of Myrtus communis L., which has traditional medicinal use for different purposes, from a broad perspective. Material and Method: The antioxidant (DPPH, ABTS, total phenol, and flavonoid amounts) anti-inflammatory (LOX enzyme inhibition), antidiabetic (α-glucosidase enzyme inhibition), and cytotoxic properties (MTT assay) of a 70% methanol extract made from leaves and dichloromethane, butanol, ethyl acetate, and the residual water fractions were investigated. Result and Discussion: The DPPH radical scavenging effect of the ethyl acetate fraction, with the highest total phenol and flavonoid content, was found to be 1.4 µg/ml, and the ABTS radical scavenging effect was 2.58 mmol/Trolox. The most potent inhibitor of LOX (IC50: 31.17 µg/ml) and α-glucosidase (96% inhibition at 0.5 mg/ml) enzymes was determined as ethyl acetate extract. Dichloromethane fraction was shown to have the most cytotoxic activity in both Hela and Colo cell lines. This research has given us a better understanding of the traditional use of the M. communis plant, which stands out for its therapeutic properties.

Nutritional Composition and Pharmacological Activity of Musa balbisiana Colla Seed: An Insight into Phytochemical and Cellular Bioenergetic Profiling.

Musa balbisiana Colla belongs to the family Musaceae which is well-known for its nutritional and pharmacological properties. Here, we have analysed the phytochemical content and evaluated the nutritional, antioxidant, anti-glycation, α-amylase, and α-glucosidase inhibition potential. Moreover, for the first time, we have studied the bioenergetic profiles of the bioactive fractions of M. balbisiana seeds extract against oxidative stress-related mitochondrial and cellular dysfunction using XFe24 extracellular flux analyzer. M. balbisiana seeds have high nutritional values with significant levels of carbohydrates, starch, protein, and minerals (Ca, Na, Mg, Cu, Fe, and Zn). Bioactivity-guided fractionation of the methanolic extract of M. balbisiana seeds revealed that the ethyl acetate fraction (EAF) showed the highest antioxidant, anti-glycation, and phytochemical content as compared to other fractions. Moreover, the EAF showed a lower α-amylase inhibition and a higher α-glucosidase inhibitory activity. Most importantly, our GC-MS analyses of EAF revealed the presence of unique and previously unreported 14 phytochemical compounds. A strong correlation between the biological activities and total phenolic/tannin content was observed. In addition, the bioactive fraction of M. balbisiana seeds (EAF) improved the bioenergetic profiles of free fatty acid-induced oxidative stress with a concomitant increase in ATP production, and respiratory and glycolytic capacity. Altogether, our findings suggest that M. balbisiana seeds can be used as a natural supplement to boost antioxidant levels and combat oxidative stress and non-enzymatic glycation.

Polyethylene glycol mediated, novel, one-pot three-component synthesis of benzimidazolyl-thiazoles as potent α-glucosidase inhibitors: Design, synthesis, molecular modelling, ADME studies

Polyethylene glycol promoted, novel, one-pot, three-component synthesis of benzimidazole based thaizole derivatives (4a-s) has been synthesized via a multi-component approach by using 5-amino-2-mercaptobenzimidazole, phenyl isothiocyanates, and substituted phenacyl bromides using PEG-400 as a recyclable and greener solvent in a shorter reaction time without any by-products. All the synthesized compounds (4a-s) were well characterized by analytical and spectroscopic techniques. Furthermore, some of the synthesized compounds were evaluated for their in-vitro α-amylase inhibition activity using Acarbose as a standard positive control. Among the tested scaffolds, compound 4d, 4c, 4 h, 4j and 4b have shown significant inhibitory activity against α-amylase enzyme with IC50 values 12.02 ± 0.56; 12.25± 0.28; 12.74 ± 0.45; 17.83 ± 0.21 and 19.10 ± 0.88 μg/mL respectively. Also we insight in to the molecular docking studies, based on the binding results, compounds 4c and 4d to have shown stable binding patterns to the human pancreatic α–amylase with montbretin A (PDBID: 4W93). The structure-activity relationship (SAR) studies of all the title scaffolds were also established. The α- amylase inhibition, molecular docking studies, molecular dynamic simulations, and drug-likeness properties (Lipinski parameters and in-silico ADME properties) of the title compounds were suggested that these are promising anti-diabetic active skeletons.