In Silico Computational Studies of Bioactive Secondary Metabolites from Wedelia trilobata against Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) Protein Associated with Cancer Cell Survival and Resistance

Molecules, Journal Year: 2023, Volume and Issue: 28(4), P. 1588 - 1588

Published: Feb. 7, 2023

In the present study, binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and dynamics simulation. The results demonstrated that energies docked compounds with Bcl-2 ranged −5.3 kcal/mol to −10.1 kcal/mol. However, lowest energy (−10.1 kcal/mol) offered Friedelin against when compared other standard drug Obatoclax (−8.4 kcal/mol). simulations revealed Friedelin-Bcl-2 complex found be stable throughout simulation period 100 ns. Overall, predicted Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties are relatively better than Obatoclax, most noticeable differences many parameters where has no AMES toxicity, hepatotoxicity, skin sensitization. ADMET profiling selected supported their drug-likeness properties. Based on computational analyses, study concluded W. potential inhibitor protein, which merits attention for further vitro vivo studies before clinical trials.

Language: Английский

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Screening for potential novel probiotic Levilactobacillus brevis RAMULAB52 with antihyperglycemic property from fermented Carica papaya L.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 20, 2023

Probiotics are live microorganisms with various health benefits when consumed in appropriate amounts. Fermented foods a rich source of these beneficial organisms. This study aimed to investigate the probiotic potential lactic acid bacteria (LAB) isolated from fermented papaya (Carica L.) through vitro methods. The LAB strains were thoroughly characterized, considering their morphological, physiological, fermentative, biochemical, and molecular properties. strain's adherence resistance gastrointestinal conditions, as well its antibacterial antioxidant capabilities, examined. Moreover, tested for susceptibility against specific antibiotics, safety evaluations encompassed hemolytic assay DNase activity. supernatant isolate underwent organic profiling (LCMS). primary objective this was assess inhibitory activity α-amylase α-glucosidase enzymes, both silico. Gram-positive that catalase-negative carbohydrate fermenting selected further analysis. exhibited bile (0.3% 1%), phenol (0.1% 0.4%), simulated juice (pH 3-8). It demonstrated potent abilities kanamycin, vancomycin, methicillin. strain showed autoaggregation (83%) adhesion chicken crop epithelial cells, buccal HT-29 cells. Safety assessments indicated no evidence hemolysis or DNA degradation, confirming isolates. isolate's identity confirmed using 16S rRNA sequence. Levilactobacillus brevis RAMULAB52, derived papaya, promising significant inhibition (86.97%) (75.87%) enzymes. In silico studies uncovered hydroxycitric acid, one acids isolate, interacted crucial amino residues target Specifically, formed hydrogen bonds key residues, such GLU233 ASP197 α-amylase, ASN241, ARG312, GLU304, SER308, HIS279, PRO309, PHE311 α-glucosidase. conclusion, possesses properties exhibits an effective remedy diabetes. Its abilities, different cell types, enzymes make it valuable candidate research application field probiotics diabetes management.

Language: Английский

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EXPLORING JACKFRUIT FLOUR POLYPHENOLS AS PROMISING SGLT-2 INHIBITORS FOR HYPERGLYCEMIA MANAGEMENT

International Journal of Applied Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 199 - 208

Published: Jan. 7, 2025

Objective: This study explored the potential of dietary polyphenols from whole green jackfruit flour as natural Sodium-Glucose Co-Transporter-2 (SGLT-2) inhibitors for managing hyperglycemia in diabetes mellitus. Methods: Advanced bio-computational techniques, including molecular docking, Molecular Dynamics (MD) simulations, and binding free energy calculations, were employed to identify assess flour. Caffeic syringic acids highlighted their strong affinities SGLT-2 receptor. Additionally, a ligand-based pharmacophore model was developed using caffeic acid reference screen new lead compounds commercial product databases. Results: The found that exhibited stronger more stable interaction profiles with receptor than standard drug empagliflozin. MD simulations demonstrated these provided greater stability site, indicating efficacy inhibitors. screening further supported findings, identifying both promising candidates. Among 14 obtained High-Performance Liquid Chromatography (HPLC), docking suggested (binding affinity:-9.0 kcal/mol) affinity:-9.1 compared empagliflozin affinity:-10.4 kcal/mol). Further, dynamics through Root mean Square Deviation (RMSD), Fluctuation (RMSF), Radius Gyration (Rg), Solvent Accessible Surface Area (SASA), ligand hydrogen bonds. Conclusion: is first effective These show significant novel agents findings support exploration plant-derived therapies treatment.

Language: Английский

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Combined in vitro and in silico approach to define alangimarckine from Thunbergia mysorensis leaves as a potential inhibitor of α-glucosidase

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 20

Published: March 6, 2025

The current work investigated biocomputational methodologies for α-glucosidase inhibition to examine the antidiabetic potential of methanolic extract T. mysorensis leaves (MeL). MeL intensely impeded yeast-glucosidase, which is vital treating postprandial hyperglycemia (IC50 = 5.76 ± 0.10 μg/mL) in comparison an acarbose control 7.98 0.23 μg/mL). affected by phytochemical profiling employing LC-MS, GC-MS, and HPLC analysis determine bioactive components responsible activity. specified phytocompounds were employed silico research following profiling, where they docked into inhibitor binding site α-glucosidase. Molecular docking simulations, molecular dynamics free energy inquiries utilized clarify mechanism block Alangimarckine a glucocorticoid that used treat nasal symptoms. inhibited target enzyme with greater efficiency (-9.7 kcal/mol) than (-8.6 during docking. Concerning simulation studies, Alangimarckine-α-glucosidase complex was found be stable inside protein, compared -α-glucosidase complex. Additionally, alangimarckine at IC50 5.32 0.19 μg/mL vitro α-glucosidase, efficient both acarbose. Therefore, our suggests from may function as potent medications. could vivo clinical investigations specify its properties inhibition.

Language: Английский

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Inhibition of carbohydrate hydrolyzing enzymes by a potential probiotic Levilactobacillus brevis RAMULAB49 isolated from fermented Ananas comosus

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: June 14, 2023

The research aimed to explore the potential probiotic characteristics of Levilactobacillus brevis RAMULAB49, a strain lactic acid bacteria (LAB) isolated from fermented pineapple, specifically focusing on its antidiabetic effects. importance probiotics in maintaining balanced gut microbiota and supporting human physiology metabolism motivated this research. All collected isolates underwent microscopic biochemical screenings, those exhibiting Gram-positive characteristics, negative catalase activity, phenol tolerance, gastrointestinal conditions, adhesion capabilities were selected. Antibiotic susceptibility was assessed, along with safety evaluations encompassing hemolytic DNase enzyme activity tests. isolate's antioxidant ability inhibit carbohydrate hydrolyzing enzymes examined. Additionally, organic profiling (LC-MS) silico studies conducted tested extracts. RAMULAB49 demonstrated desired such as Gram-positive, hydrophobicity (65.71%), autoaggregation (77.76%). Coaggregation against Micrococcus luteus, Pseudomonas aeruginosa, Salmonella enterica serovar Typhimurium observed. Molecular characterization revealed significant ABTS DPPH inhibition rates 74.85% 60.51%, respectively, at bacterial cell concentration 109 CFU/mL. cell-free supernatant exhibited substantial α-amylase (56.19%) α-glucosidase (55.69%) vitro. In supported these findings, highlighting inhibitory effects specific acids citric acid, hydroxycitric malic which displayed higher Pa values compared other compounds. These outcomes underscore promising pineapple. Its properties, including antimicrobial autoaggregation, contribute therapeutic application. activities further support anti-diabetic properties. analysis identified that may observed isolate derived holds promise an agent for managing diabetes. Further investigations should focus evaluating efficacy vivo consider application diabetes management.

Language: Английский

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Quinoline- and Isoindoline-Integrated Polycyclic Compounds as Antioxidant, and Antidiabetic Agents Targeting the Dual Inhibition of α-Glycosidase and α-Amylase Enzymes

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(9), P. 1222 - 1222

Published: Aug. 30, 2023

Novel analogs of quinoline and isoindoline containing various heterocycles, such as tetrazole, triazole, pyrazole, pyridine, were synthesized characterized using FT-IR, NMR, mass spectroscopy, their antioxidant antidiabetic activities investigated. The previously compound 1 was utilized in conjugation with ketone-bearing tetrazole isoindoline-1,3-dione to synthesize Schiff’s bases 2 3. Furthermore, hydrazide treated aryledines provide pyrazoles 4a–c. Compound 5 obtained by treating potassium thiocyanate, which then cyclized a basic solution afford triazole 6. On the other hand, pyridine derivatives 7a–d 8a–d 2-(4-acetylphenyl)isoindoline-1,3-dione via one-pot condensation reaction aryl aldehydes active methylene compounds. From studies, 7d showed significant activity an EC50 = 0.65, 0.52, 0.93 mM free radical scavenging assays (DPPH, ABTS, superoxide anion radicals). It also displayed noteworthy inhibitory against both enzymes α-glycosidase (IC50: 0.07 mM) α-amylase (0.21 compared acarbose (0.09 0.25 for α-amylase), higher than During silico assays, exhibited favorable binding affinities towards (−10.9 kcal/mol) (−9.0 (−8.6 kcal/mol −6.0 α-amylase). stability demonstrated molecular dynamics simulations estimations energy throughout simulation session (100 ns).

Language: Английский

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Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(1), P. e0296010 - e0296010

Published: Jan. 24, 2024

The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, dynamics (MD) simulation and MM-PBSA approach. result docking confirmed that out 200 screened, three such as Harzianelactone A, Pretrichodermamide G Aspochalasin M, potentially bound with active binding site EGFR domain(PDB ID: 1M17) a threshold score ≤– 9.0 kcal/mol when compared standard inhibitor (Erlotinib). MD was run to investigate potential for stable complex formation domain-unbound/lead metabolite (Aspochalasin M)-bound/standard (Erlotinib)-bound complex. analysis at 100 ns revealed M formed EGFR. Besides, silico predication pharmacokinetic properties further qualified drug-likeness rules no harmful side effects ( viz ., hERG toxicity, hepatotoxicity skin sensitization), non-mutagenicity favourable logBB value. Moreover, BOILED-Egg model predicted showed higher gastrointestinal absorption improved bioavailability administered orally removed from central nervous system (CNS). results computational studies concluded possessed significant EGFR’s sites known Therefore, can be used possible anticancer drug candidate vitro vivo experimental validation are required determine its potential.

Language: Английский

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Sustainable synthesis of zinc oxide nanoparticles using Piper betle petiole leaf extract: Antibacterial, antioxidant, and cytotoxic potential

Results in Chemistry, Journal Year: 2024, Volume and Issue: 9, P. 101646 - 101646

Published: July 1, 2024

The present study used Piper betle petiole leaf extract as an efficient reducing agent to produce zinc oxide nanoparticles (ZnO NPs). change in the color of reaction mixture from brown white indicates formation ZnO NPs, which is also noticed UV–Visible spectral analysis (peak at 320 nm). Investigations using X-ray diffraction (XRD) revealed that particles were crystalline. Additionally, scanning electron microscopy (SEM), Energy Dispersive (EDAX), dynamic light scattering (DLS), and Fourier transform infrared (FTIR) techniques understand structural, elemental aspects as-prepared NPs. antibacterial activity NPs was assessed disc diffusion approach method against clinical strains Escherichia coli, Pseudomonas fluorescence, Micrococcus luteus, Bacillus subtilis. zone inhibition minimum inhibitory indices (MIC) this process. showed strong effects. In addition, anticancer efficacy material tested MDA-MB-231 breast cancer cell lines, results potent inhibiting growth cells. mechanistic evaluation such carried out silico methods suggested anti-breast L-ZnONPs mediated by human HER2 kinase domain. This suggests preparation plant sources can be excellent producing biomedical goods are both environmentally friendly versatile.

Language: Английский

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A computational odyssey: uncovering classical β-lactamase inhibitors in dry fruits

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 42(9), P. 4578 - 4604

Published: June 8, 2023

In the antibacterial arsenal, β-lactams have held a prominent position, but increasing resistance due to unauthorized use and genetic factors requires new strategies. Combining β-lactamase inhibitors with broad-spectrum proves effective in combating this resistance. ESBL producers demand inhibitors, leading exploration of plant-derived secondary metabolites for potent β-lactam antibiotics or alternative inhibitors. Using virtual screening, molecular docking, ADMET analysis, dynamic simulation, study actively analyzed inhibitory activity figs, cashews, walnuts, peanuts against SHV-1, NDM-1, KPC-2, OXA-48 β-lactamases. AutoDock Vina, docking affinities various compounds target enzymes were initially screened, revealing 12 bioactive higher compared Avibactam Tazobactam. Top-scoring metabolites, including Oleanolic acid, Protocatechuic Tannin, subjected MD simulation studies further analyze stability docked complexes using WebGro. The coordinates, terms RMSD, RMSF, SASA, Rg, hydrogen bonds formed, showed that these phytocompounds are stable enough retain active sites at orientations. PCA FEL analysis also motion Cα residues phytochemical-bound enzymes. pharmacokinetic top phytochemicals was performed their bioavailability toxicity. This provides insights into therapeutic potential selected dry fruits contributes future experimental identify βL from plants.Communicated by Ramaswamy H. Sarma

Language: Английский

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Conformationally Flexible Ellagitannins: Conformational Analysis of Davidiin and Punicafolin via DFT Calculation of 1H NMR Coupling Constants

Published: Sept. 21, 2023

Many ellagitannins with various conformations of their glucose moiety have been isolated from natural sources. Here, a conformational analysis was performed via the density functional theory calculation 1H NMR coupling constants. It observed that, in solution state, davidiin exists as an equilibrium mixture BO,3 (boat) and 1C4 (chair) states, while punicafolin is 3S1 (skew-boat) states. Their states changed depending on solvent temperature. Such flexibility may be important for biosynthesis diverse structures.

Language: Английский

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