Effect of Phenol and Alkylamide Interaction on α-Glucosidase Inhibition and Cellular Antioxidant Activity during In Vitro Digestion: Using Szechuan Pepper (Zanthoxylum genus) as a Model.

Although recent evidence indicated significant phenol and alkylamide interaction in aqueous solutions, the gastrointestinal digestion influence of the combination remains unclear. This study aims to investigate phenol and alkylamide interaction during in vitro digestion, focusing on bioaccessibility and bioactivity, including α-glucosidase inhibition and cellular antioxidant activity. Additionally, the structural mechanism of phenol and alkylamide interaction during in vitro digestion was explored. The results indicated that the presence of phenols and alkylamides significantly increased or decreased their respective bioaccessibility, depending on the Zanthoxylum varieties. Furthermore, although antagonistic phenol/alkylamide interaction was evident during α-glucosidase inhibition, cellular oxidative stress alleviation, and antioxidant gene transcription upregulation, this effect weakened gradually as digestion progressed. Glycoside bond cleavage and the methylation of phenols as well as alkylamide isomerization and addition were observed during digestion, modifying the hydrogen bonding sites and interaction behavior. This study provided insights into the phenol/alkylamide interaction in the gastrointestinal tract.

New α-Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Efficient biotransformation of naringenin to naringenin α-glucoside, a novel α-glucosidase inhibitor, by amylosucrase from Deinococcus wulumuquiensis.

Amylosucrase (ASase) efficiently biosynthesizes α-glucoside using flavonoids as acceptor molecules and sucrose as a donor molecule. Here, ASase from Deinococcus wulumuqiensis (DwAS) biosynthesized more naringenin α-glucoside (NαG) with sucrose and naringenin as donor and acceptor molecules, respectively, than other ASases from Deinococcus sp. The biotransformation rate of DwAS to NαG was 21.3% compared to 7.1-16.2% for other ASases. Docking simulations showed that the active site of DwAS was more accessible to naringenin than those of others. The 217th valine in DwAS corresponded to the 221st isoleucine in Deinococcus geothermalis AS (DgAS), and the isoleucine possibly prevented naringenin from accessing the active site. The DwAS-V217I mutant had a significantly lower biosynthetic rate of NαG than DwAS. The kcat/Km value of DwAS with naringenin as the donor was significantly higher than that of DgAS and DwAS-V217I. In addition, NαG inhibited human intestinal α-glucosidase more efficiently than naringenin.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies.

Two α-pyrone analogs were isolated from the endophytic fungus Diaporthe sp. CB10100, which is derived from the medicinal plant Sinomenium acutum. These analogs included a new compound, diaporpyrone F (3), and a known compound, diaporpyrone D (4). The structure of 3 was identified by a comprehensive examination of HRESIMS, 1D and 2D NMR spectroscopic data. Bioinformatics analysis revealed that biosynthetic gene clusters for α-pyrone analogs are common in fungi of Diaporthe species. The in vitro α-glucosidase inhibitory activity and antibacterial assay of 4 revealed that it has a 46.40% inhibitory effect on α-glucosidase at 800 µM, while no antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycolicibacterium (Mycobacterium) smegmatis or Klebsiella pneumoniae at 64 µg/mL. Molecular docking and molecular dynamics simulations of 4 with α-glucosidase further suggested that the compounds are potential α-glucosidase inhibitors. Therefore, α-pyrone analogs can be used as lead compounds for α-glucosidase inhibitors in more in-depth studies.

Anti-Inflammatory and α-Glucosidase Inhibitory Triterpenoid with Diverse Carbon Skeletons from the Fruits of Rosa roxburghii.

The fruits of Rosa roxburghii Tratt. are edible nutritional food with high medicinal value and have been traditionally used as Chinese folk medicine for a long time. In this study, 26 triterpenoids including four new pentacyclic triterpenoids, roxbuterpenes A-D (1, 4, 5, and 24), along with 22 known analogues (2, 3, 6-23, 25, and 26), were isolated from the fruits of R. roxburghii. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, HRESIMS and NMR spectroscopy). The absolute configuration of roxbuterpene A (1) was determined by an X-ray crystallographic analysis. This is the first report of the crystal structure of 5/6/6/6/6-fused system pentacyclic triterpenoid. Notably, roxbuterpenes A and B (1 and 4) possessed the A-ring contracted triterpenoid and nortriterpenoid skeletons with a rare 5/6/6/6/6-fused system, respectively. Compounds 1-7, 11, 13-15, 18-20, 24, and 25 exhibited moderate or potent inhibitory activities against α-glucosidase. Compounds 2, 4, 6, 11, and 14 showed strong activities against α-glucosidase with IC50 values of 8.4 ± 1.6, 7.3 ± 2.2, 13.6 ± 1.4, 0.9 ± 0.4, and 12.5 ± 2.4 µM, respectively (positive control acarbose, 10.1 ± 0.8 µM). Compounds 13, 14, and 16 moderately inhibited the release of NO (nitric oxide) with IC50 values ranging from 25.1 ± 2.0 to 51.4 ± 3.1 µM. Furthermore, the expressions of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) were detected by ELISA (enzyme-linked immunosorbent assay), and compounds 13, 14, and 16 exhibited moderate inhibitory effects on TNF-α and IL-6 release in a dose-dependent manner ranging from 12.5 to 50 µM.

Xanthones with multiple roles against diabetes: their synthesis, structure-activity relationship, and mechanism studies.

A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 µM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 µM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 µM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.

Rapid screening of the novel bioactive peptides with notable α-glucosidase inhibitory activity by UF-LC-MS/MS combined with three-AI-tool from black beans.

This work aimed to propose a rapid method to screen the bioactive peptides with anti-α-glucosidase activity instead of traditional multiple laborious purification and identification procedures. 242 peptides binding to α-glycosidase were quickly screened and identified by bio-affinity ultrafiltration combined with LC-MS/MS from the double enzymatic hydrolysate of black beans. Top three peptides with notable anti-α-glucosidase activity, NNNPFKF, RADLPGVK and FLKEAFGV were further rapidly screened and ranked by the three artificial intelligence tools (three-AI-tool) BIOPEP database, PeptideRanker and molecular docking from the 242 peptides. Their IC50 values were in order as 4.20 ± 0.11 mg/mL, 2.83 ± 0.03 mg/mL, 1.32 ± 0.09 mg/mL, which was opposite to AI ranking, for the hydrophobicity index of the peptides was not included in the screening criteria. According to the kinetics, FT-IR, CD and ITC analyses, the binding of the three peptides to α-glucosidase is a spontaneous and irreversible endothermic reaction that results from hydrogen bonds and hydrophobic interactions, which mainly changes the α-helix structure of α-glucosidase. The peptide-activity can be evaluated vividly by AFM in vitro. In vivo, the screened FLKEAFGV and RADLPGVK can lower blood sugar levels as effectively as acarbose, they are expected to be an alternative to synthetic drugs for the treatment of Type 2 diabetes.

Inhibition of α-glucosidase activity and intestinal glucose transport to assess the in vivo anti-hyperglycemic potential of dodecyl-acylated phlorizin and polydatin derivatives.

A diet containing natural active compounds that can inhibit the hydrolytic activity of α-glucosidase on carbohydrates and intestinal glucose absorption is an effective means of controlling postprandial hyperglycemia. Phlorizin and polydatin as phenolic glycosides have a high affinity for the catalytic site of α-glucosidase, but exhibited unsatisfactory competitive inhibitory capacity, with an IC50 of 0.97 and >2 mM, respectively. However, dodecyl-acylated derivatives of phlorizin and polydatin exerted α-glucosidase inhibitory capacity, with an IC50 of 55.10 and 70.95 µM, respectively, which were greatly enhanced and much stronger than that of acarbose with an IC50 of 2.46 mM. The SPR assay suggested the high affinity of dodecyl phlorizin and dodecyl polydatin to α-glucosidase with equilibrium dissociation constant (KD) values of 12.0 and 7.9 µM, respectively. Both dodecyl phlorizin and dodecyl polydatin reduced the catalytic ability of α-glucosidase by reversible noncompetitive and uncompetitive mixed inhibition, which bind noncovalently to the allosteric site 2 through hydrogen bonds and hydrophobic interactions, thereby inducing the secondary structure unfolding and intrinsic fluorescence quenching of α-glucosidase. Confocal microscopy detection visually showed significant inhibitory effects on FITC-labeled glucose uptake in intestinal Caco-2 cells by phlorizin, polydatin, dodecyl phlorizin and dodecyl polydatin. In addition, based on the differentiated Caco-2 cell monolayer model, dodecyl phlorizin and dodecyl polydatin suppressed intestinal glucose transport more effectively than phlorizin and polydatin, suggesting that they were promising in vivo hypoglycemic active compounds.

Efficient degradation and enhanced α-glucosidase inhibitory activity of apricot polysaccharides through non-thermal plasma assisted non-metallic Fenton reaction.

Dielectric barrier discharge (DBD) was a commonly used non-thermal plasma (CP) technology. This paper aimed to enhance the biological activity of apricot polysaccharides (AP) by using dielectric barrier discharge (DBD-CP) assisted H2O2-VC Fenton reaction for degradation. The degradation conditions were optimized through response surface methodology. The molecular weight (Mw) of degraded apricot polysaccharides (DAP) was 19.71 kDa, which was 7.25 % of AP. The inhibition rate of DAP (2 mg/mL) was 82.8 ± 3.27 %, which was 106.87 % higher than that of AP. DBD-CP/H2O2-VC degradation changed the monosaccharide composition of AP and improved the linearity of polysaccharide chains. In addition, a novel apricot polysaccharide DAP-2 with a Mw of only 6.60 kDa was isolated from DAP. The repeating units of the main chain of DAP-2 were →4)-α-D-GalpA-(1 →, the branch chain was mainly composed of α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→ connected to O-3 position →3,4)-α-D-GalpA-(1→. The complex structure formed by the combination of DAP-2 and α-glucosidase was stable. DAP-2 had a higher α-glucosidase binding ability than the acarbose. These results suggested that DAP-2 had the potential to be developed as a potential hypoglycemic functional food and drug.

Extraction, identification, and molecular mechanisms of α-glucosidase inhibitory peptides from defatted Antarctic krill (Euphausia superba) powder hydrolysates.

The objective of this study was to explore the potential of Antarctic krill-derived peptides as α-glucosidase inhibitors for the treatment of type 2 diabetes. The enzymolysis conditions of α-glucosidase inhibitory peptides were optimized by response surface methodology (RSM), a statistical method that efficiently determines optimal conditions with a limited number of experiments. Gel chromatography and LC-MS/MS techniques were utilized to determine the molecular weight (Mw) distribution and sequences of the hydrolysates. The identification and analysis of the mechanism behind α-glucosidase inhibitory peptides were conducted through conventional and computer-assisted techniques. The binding affinities between peptides and α-glucosidase were further validated using BLI (biolayer interferometry) assay. The results revealed that hydrolysates generated by neutrase exhibited the highest α-glucosidase inhibition rate. Optimal conditions for hydrolysis were determined to be an enzyme concentration of 6 × 103 U/g, hydrolysis time of 5.4 h, and hydrolysis temperature of 45 °C. Four peptides (LPFQR, PSFD, PSFDF, VPFPR) with strong binding affinities to the active site of α-glucosidase, primarily through hydrogen bonding and hydrophobic interactions. This study highlights the prospective utility of Antarctic krill-derived peptides in curtailing α-glucosidase activity, offering a theoretical foundation for the development of novel α-glucosidase inhibitors and related functional foods to enhance diabetes management.

Natural Sweetener, Glycyrrhetinic Acid 3-O-Mono-beta-d-glucuronide, for Postprandial Hyperglycemia Management.

This study examines the inhibitory effects of a range of sweeteners on α-glucosidase. Our findings revealed that only one natural sweetener, namely, glycyrrhetinic acid 3-O-mono-beta-d-glucuronide (GAMG), derived from licorice, exhibited a mixed-type inhibition against α-glucosidase with a IC50 value of 0.73 ± 0.05 mg/mL. The fluorescence intensity of α-glucosidase was quenched by GAMG in the formation of an α-glucosidase-GAMG complex. GAMG has been shown to induce conformational changes in α-glucosidase, likely through hydrogen bonding, van der Waals force, and alkyl-alkyl interactions with amino acid residues, including Arg 281, Leu 283, Trp 376, Asp 404, Asp 443, Trp 481, Asp 518, Phe 525, Ala 555, and Asp 616. Additional animal validation experiments demonstrated that GAMG slowed starch digestion, thereby attenuating the postprandial glycemic response. Taken together, these findings provide evidence that GAMG is a natural sweetener with potent inhibitory activity that selectively targets α-glucosidase. This study supports the use of GAMG as a natural sweetener, which holds a high biological value and may be beneficial for managing postprandial hyperglycemia.

Phenolic Glycosides from Viburnum chinshanense Leaves and their α-Amylase and α-Glucosidase Inhibitory Activity.

The phytochemical investigation of Viburnum chinshanense leaves led to the isolation and identification of four new phenolic glycosides, viburninsides A-D (1-4), and eight known analogues (5-12). The structures of the four undescribed compounds were determined by spectroscopic techniques, including 1D NMR, 2D NMR, and HRESIMS, and their containing sugar units were confirmed by acid hydrolysis and HPLC analysis of the monosaccharide's chiral derivatives. Additionally, the α-amylase and α-glucosidase inhibitory activities of the isolated compounds were assessed. Compounds 1, 2, 4, 9, and 10 exhibited potential inhibitory activities against α-amylase and α-glucosidase with IC50 values ranging from 35.07 µM to 47.42 µM and 18.27 µM to 43.65 µM, respectively. Molecular docking analysis of compound 4 with the strongest inhibition against the target enzymes was also conducted.

Phytochemical analyses by LC-HRMS, FTIR spectral analysis, antioxidant, antidiabetic and antityrosinase activity of Crataegus orientalis Pall. ex M. Bieb fruit extracted with various solvents.

BACKGROUND: Crataegus orientalis Pall. ex M. Bieb fruit (COPMB) is extensively used as a source of various products in the medicinal-aromatic field and holds the potential for erosion control, ornamental purposes, food source, and economic benefits for forest villagers from its fruits. This study aims to determine the chemical components and biological activities of extracts prepared from COPMB using different solvents. RESULTS: The present work was designed to define the antioxidant activity [phosphomolybdenum (total antioxidant capacity), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric ion-reducing antioxidant capacity (CUPRAC) and metal chelating activity (MCA)], phytochemical screening analysis, enzyme inhibitor (α-amylase, α-glucosidase and tyrosinase) potential, and liquid chromatography-high resolution mass spectrometry (LC-HRMS) secondary metabolite profiling in different extracts of COPMB. The results of LC-HRMS revealed that fumaric acid was the main phenolic compound in all extracts. Among the extracts, ethyl acetate extract has the highest phytochemical and antioxidant properties [total phenolic content (TPC): 32.5 mg GAE/g, total flavonoid content (TFC): 12.2 mg QE/g, ABTS: 213.0 mg TE/g; CUPRAC: 126.0 mg TE/g, MCA: 145.0 mg EDTA/g; FRAP: 122.8 mg TE/g; TAC: 2.8 mmol TE/g]. Ethyl acetate and methanol extracts are more effective in α-amylase (0.27 ± 0.01 mg/mL; 0.12 ± 0.00 mg/mL), α-glucosidase (0.63 ± 0.02 mg/mL; 0.77 ± 0.02 mg/mL) and tyrosinase (0.03 ± 0.00 mg/mL; 0.03 ± 0.00 mg/mL) enzyme inhibition potentials compared to standard acarbose (0.75 ± 0.02 mg/mL for α-amylase; 1.11 ± 0.03 mg/mL for α-glucosidase) and kojic acid (0.04 ± 0.00 mg/mL). CONCLUSION: The findings from this study suggest that COPMB could serve as a valuable source of natural agents for the food and pharmaceutical industry. © 2024 Society of Chemical Industry.

Design and synthesis of 2-amino-4,6-diarylpyrimidine derivatives as potent α-glucosidase and α-amylase inhibitors: structure-activity relationship, in vitro, QSAR, molecular docking, MD simulations and drug-likeness studies.

In the present study, a series of 2-amino-4,6-diarylpyrimidine derivatives was designed, synthesized, characterized and evaluated for their in vitro α-glucosidase and α-amylase enzyme inhibition assays. The outcomes proved that this class of compounds exhibit considerable inhibitory activity against both enzymes. Among the target compounds, compounds 4p and 6p demonstrated the most potent dual inhibition with IC50 = 0.087 ± 0.01 µM for α-glucosidase; 0.189 ± 0.02 µM for α-amylase and IC50 = 0.095 ± 0.03 µM for α-glucosidase; 0.214 ± 0.03 µM for α-amylase, respectively as compared to the standard rutin (IC50 = 0.192 ± 0.02 µM for α-glucosidase and 0.224 ± 0.02 µM for α-amylase). Remarkably, the enzyme inhibition results indicate that test compounds have stronger inhibitory effect on the target enzymes than the positive control, with a significantly lower IC50 value. Moreover, these series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type manner with IC50 between 0.087 ± 0.01 µM to 1.952 ± 0.26 µM. Furthermore, molecular docking studies were performed to affirm the binding interactions of this scaffold to the active sites of α-glucosidase and α-amylase enzymes. The quantitative structure-activity relationship (QSAR) investigations showed a strong association between 1p-15p structures and their inhibitory actions (IC50) with a correlation value (R2) of 0.999916. Finally, molecular dynamic (MD) simulations were carried out to assess the dynamic behavior, stability of the protein-ligand complex, and binding affinity of the most active inhibitor 4p. The experimental and theoretical results therefore exposed a very good compatibility. Additionally, the drug-likeness assay revealed that some compounds exhibit a linear association with Lipinski's rule of five, indicating good drug-likeness and bioactivity scores for pharmacological targets.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization, X-ray, α-glucosidase inhibition and molecular docking study of new triazolic systems based on 1,5-benzodiazepine via 1,3-dipolar cycloaddition reactions.

We report in this work a synthesis of novel triazolo[1,5]benzodiazepine derivatives by the 1,3-dipolar cycloaddition reaction of N-aryl-C-ethoxycarbonylnitrilimines with 1,5-benzodiazepines. All the structures of the new compounds were determined from their NMR (1H and 13C) and HRMS. Then, X-ray crystallography analysis of compound 4d confirmed the stereochemistry of cycloadducts. The compounds 1, 4a-d, 5a-d, 6c, 7 and 8 were evaluated for their in vitro anti-diabetic activity against α-glucosidase. The compounds 1, 4d, 5a and 5b showed potential inhibitory activities compared to standard acarbose. Additionally, an in silico docking study was conducted to look into the active binding mode of the synthesized compounds within the target enzyme.Communicated by Ramaswamy H. Sarma.

Assessment of the Anti-Breast Cancer Effects of Urolithin with Molecular Docking Studies in the In Vitro Condition: Introducing a Novel Chemotherapeutic Drug.

A lot of research has been done on using natural items as diabetes treatment. The molecular docking study was conducted to evaluate the inhibitory activities of urolithin A against α-amylase, α-glucosidase, and aldose reductase. The molecular docking calculations indicated the probable interactions and the characteristics of these contacts at an atomic level. The results of the docking calculations showed the docking score of urolithin A against α-amylase was -5.169 kcal/mol. This value for α-glucosidase and aldose reductase was -3.657 kcal/mol and -7.635 kcal/mol, respectively. In general, the outcomes of the docking calculations revealed that urolithin A can construct several hydrogen bonds and hydrophobic contacts with the assessed enzymes and reduces their activities considerably. The properties of urolithin against common human breast cancer cell lines, i.e., SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE were evaluated. The IC50 of the urolithin was 400, 443, 392, 418, 397, 530, 566 and 551 against SkBr3, MDA-MB-231, MCF-7, Hs578T, Evsa-T, BT-549, AU565 and 600MPE, respectively. After doing the clinical trial studies, the recent molecule may be used as an anti-breast cancer supplement in humans. IC50 values of urolithin A on α-amylase, α-glucosidase, and aldose reductase enzymes were obtained at 16.14, 1.06 and 98.73 µM, respectively.

Molecular dynamics study of stigmasterol and beta-sitosterol of Morinda citrifolia L. towards α-amylase and α-glucosidase.

Previous in vivo studies of Morinda citrifolia (Rubiaceae) reported that the extract inhibited α-amylase and reduced blood glucose levels in streptozotocin-induced diabetes mice. Moreover, molecular docking studies confirmed that ursolic acid and sterol compounds contained in the fruit interacted with important residues in the binding site of α-amylase and α-glucosidase. Our work aimed to study the complex stability of stigmasterol (which has been isolated from the M. citrifolia fruit for the first time) and beta-sitosterol towards α-amylase and α-glucosidase by employing molecular dynamics simulation on GROMACS 2016.3 embedded with the AMBER99SB-ILDN force field. The simulation was carried out for 100 ns at 310 oK. Based on the RMSD and RMSF graphs, the complexes of stigmasterol/α-amylase and stigmasterol/α-glucosidase are more stable compared to acarbose, the known inhibitor of both enzymes. Moreover, beta-sitosterol indicates a better stability complex with α-glucosidase compared to that of acarbose. Interestingly, the affinity of stigmasterol and beta-sitosterol to both enzymes, in terms of the total binding energy, is stronger than that of acarbose. Taken together, stigmasterol and beta-sitosterol in M. citrifolia fruit may have the potency to be developed as α-amylase and α-glucosidase inhibitors.Communicated by Ramaswamy H. Sarma.

Discovery of N-(phenylsulfonyl)thiazole-2-carboxamides as potent α-glucosidase inhibitors.

In a search for novel nonsugar α-glucosidase inhibitors for diabetes treatment, a series of N-(phenylsulfonyl)thiazole-2-carboxamide derivatives were designed and synthesized, the α-glucosidase inhibitory activities were then evaluated. Several compounds with promising α-glucosidase inhibitory effects were identified. Among these, compound W24 which shows low cytotoxicity and good α-glucosidase inhibitory activity with an IC50 value of 53.0 ± 7.7 µM, is more competitive compared with the commercially available drug acarbose (IC50 = 228.3 ± 9.2 µM). W24 was identified as a promising candidate in the development of α-glucosidase inhibitors. Molecular docking studies and molecular dynamics simulation were also performed to reveal the binding pattern of the active compound to α-glucosidase, and the binding free energy of the best compound W24 was 36.3403 ± 3.91 kcal/mol.

Therapeutic properties, biological effects, antiliver cancer, and anticolon cancer effects of some natural compounds: A biochemical approach.

Natural compounds, such as carotenoids, flavonoids, anthocyanins, or terpenoids, are physiologically active components found in plants (pigments), often known as phytochemicals or phytonutrients. The in vitro cytotoxic and anticolon cancer effects of biologically bavachin, bavachinin, artepillin C, and aromadendrin compounds against SW48, SNU-C1, COLO 205, RKO, LS411N, and SW1417 cancer cell lines were assessed. Results of enzymes and antibacterial, antifungal were in level of micromolar that is good impacts. These natural compounds may be antidiabetic, anticancer, and antibacterial candidates for drug design. IC50 results were obtained between 14-19 and 5-119 µM for α-amylase and α-glucosidase, respectively. Good inhibitor Bavachinin was detected for both enzymes (IC50 for α-amylase: 14.37 µM and IC50 for α-glucosidase: 5.27 µM). The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against pancreatic α-amylase and α-glucosidase were assessed by conducting the molecular docking study. The chemical activities of aromadendrin, artepillin C, bavachin, and bavachinin against some of the expressed surface receptor proteins (CD44, CD47, CXCR4, EGFR, folate receptor, HER2, and endothelin receptor) in the mentioned cell lines were investigated using the molecular docking calculations. The results illustrated the atomic-level properties and potential interactions. These chemicals have high binding affinities to the enzymes and proteins, according to the docking scores. In addition, the compounds formed strong contacts with the enzymes and receptors. Thus, these compounds could be potential inhibitors for enzymes and cancer cells.