Exploring innovative strategies for identifying anti-breast cancer compounds by integrating 2D/3D-QSAR, molecular docking analyses, ADMET predictions, molecular dynamics simulations, and MM-PBSA approaches

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1320, P. 139500 - 139500

Published: July 31, 2024

Language: Английский

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Exploring novel and potent glycogen synthase kinase-3β inhibitors through systematic drug designing approach

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 3, 2025

Significant implications of glycogen synthase kinase-3β (GSK-3β) have been reported in various neuronal disorders and malignant cancers. GSK-3β modulates diverse protein targets through phosphorylation, its aberrant activity leads to neurological complications as well tumour onset. Therefore, inhibiting active-site fitting molecules may offer a favourable strategy for intercepting these disorders. This comprehensive study used multiple assays tandem order explore the most potent inhibitor. Following structural similarity screening, 135 molecular docking standard MM-GBSA experiments were performed using AZD1080, known inhibitor standard. Among 32 demonstrating stronger binding affinity than reference, only two chosen their free energy was compared AZD1080 Desmond trajectory clustering eventual MM-GBSA. Additionally, interaction status with explored post-molecular dynamics. The stability strongest molecule (most potent) evaluated active site above-mentioned kinase keeping apo-form reference. Notably, e-Pharmacophores mapping address level complementarity functional GSK-3β. Using techniques, we identified PubChem CID: 11167509 obstructing GSK-3β, which serve promising therapeutic after meticulous evaluation on models.

Language: Английский

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In silico exploration of natural xanthone derivatives as potential inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication and cellular entry

Journal of Computer-Aided Molecular Design, Journal Year: 2025, Volume and Issue: 39(1)

Published: Feb. 17, 2025

Language: Английский

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Network pharmacology exploring the mechanistic role of indirubin phytoconstituent from Indigo naturalis targeting GSK-3 β in Alzheimer’s disease

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: March 4, 2025

One of the most common causes dementia in older adults is Alzheimer's disease (AD). Numerous mechanisms, including acetylcholine breakdown, amyloid beta buildup, neurofibrillary tangle accumulation, and inflammation, are involved pathogenesis AD. Different targets have been demonstrated studies to alleviate cognitive impairment In AD, β impairs phosphatidylinositol-3 (PI3)/Akt signaling, activating GSK-3β. This sequence leads an increase phosphorylation tau, creation tangles, neuronal death, loss synapses, memory impairments, all which typical symptoms seen brains individuals with Using network pharmacology, molecular docking, MD simulations, we determined that indirubin can selectively interact glycogen synthase kinase 3 (GSK-3β). Traditional Chinese Medicine, Indigo naturalis, known ability control chronic diseases having as main phytoconstituent. The binding energy was -10.9 kcal/mol, better than reference ligand -9.4 kcal/mol. According indirubin-GSK-3β complex remained stable during simulation, exhibiting RMSD 1.90 comparison 2.01 2.34 for reference-GSK-3β free protein, respectively. our study, phytoconstituent from GSK-3β additional investigation quest inhibitors this crucial biological target required further in-vitro/in-vivo experimental validations.

Language: Английский

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Discovering potent GSK3β inhibitors in Rosmarinus officinalis L. for Alzheimer’s disease using homology modeling, molecular docking, MD simulation

Network Modeling Analysis in Health Informatics and Bioinformatics, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 25, 2025

Language: Английский

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Searching potential GSK-3β inhibitors from marine sources using atomistic simulations

Molecular Diversity, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

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Silk-based microparticles for the adsorption of methylene blue: formulations, characterization, adsorption study, in silico molecular docking, and molecular dynamics simulation

RSC Advances, Journal Year: 2025, Volume and Issue: 15(18), P. 14042 - 14057

Published: Jan. 1, 2025

Although silk-derived biomaterials have garnered attention for environmental remediation due to their sustainability, biocompatibility, and biodegradability, the application of silk fibroin-based microparticles (FNP) pollutant dye adsorption remains vastly underexplored. Hence, this study pioneers fabrication characterization FNP removal methylene blue (MB), offering a comprehensive comparison with two other silk-based states raw cocoon pieces (SC) sericin-degummed fibers (SD). Remarkably, achieved an capacity 122.98 mg g-1, over 32-fold higher than both SC SD (3.8 g-1), highlighting its superior efficiency. The performance was strongly influenced by experimental variables including pH, contact time, initial concentration, adsorbent dosage. Structurally, exhibited favorable physicochemical properties adsorption, uniform spherical morphology (∼2.45 μm), moderate surface area (21.894 m2 mesoporous-to-macroporous structure (pore diameter 21.911 Å), point zero charge (pHpzc) 6.7, contributing effective electrostatic interactions cationic MB. Importantly, data fitted Dubinin-Radushkevich isotherm, indicating chemisorption-dominated mechanism. Molecular docking further revealed specific fibroin-dye at Lys62 (hydrogen bonding, -0.2 kcal mol-1) Glu94 (ionic -1.9 mol-1). Additionally, molecular dynamics simulations in water confirmed results demonstrated aqueous stability fibroin-MB complex. Conclusively, work not only establishes as high-performance, eco-friendly MB removal, but also provides mechanistic insights level, scientific foundation rational design protein-based adsorbents future technologies.

Language: Английский

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β-Caryophyllene (CB2 agonist) mitigates rotenone-induced neurotoxicity and apoptosis in SH-SY5Y neuroblastoma cells via modulation of GSK-3β/NRF2/HO-1 axis

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 23, 2025

Language: Английский

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Capture-SELEX-based screening and mechanism analysis for the dual-colorimetric aptasening of microcystin in water

Analytica Chimica Acta, Journal Year: 2025, Volume and Issue: unknown, P. 344261 - 344261

Published: May 1, 2025

Language: Английский

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Antiviral effect of fucoxanthin obtained from Sargassum siliquastrum (Fucales, Phaeophyceae) against severe acute respiratory syndrome coronavirus 2

ALGAE, Journal Year: 2023, Volume and Issue: 38(4), P. 295 - 306

Published: Dec. 15, 2023

Human coronavirus diseases, particularly severe acute respiratory syndrome 2, still remain a persistent public health issue, and many recent studies are focusing on the quest for new leads against coronaviruses. To contribute to this growing pool of knowledge explore available marine natural products coronaviruses, study investigated antiviral effects fucoxanthin isolated from Sargassum siliquastrum—a brown alga found Jeju Island, South Korea. The were confirmed in 2-infected Vero cells, its structural characteristics verified silico using molecular docking dynamic simulations vitro colorimetric method. Fucoxanthin inhibited infection concentration-dependent manner, without showing cytotoxicity. Molecular revealed that binds angiotensinconverting enzyme 2-spike protein (binding energy -318.306 kcal mol^-1) main protease -205.118 mol^-1). Moreover, showed remains docked angiotensin-converting 20 ns, whereas it breaks away after 3 ns. Also, prediction was through method by inhibiting binding between 2 spike manner. These results indicate exhibits blocking entry virus. Therefore, S. siliquastrum can be potential candidate treating infection.

Language: Английский

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