New Insights into Antioxidant Peptides: An Overview of Efficient Screening, Evaluation Models, Molecular Mechanisms, and Applications

Antioxidants, Год журнала: 2024, Номер 13(2), С. 203 - 203

Опубликована: Фев. 5, 2024

Antioxidant peptides are currently a hotspot in food science, pharmaceuticals, and cosmetics. In different fields, the screening, activity evaluation, mechanisms, applications of antioxidant pivotal areas research. Among these topics, efficient screening stands at forefront cutting-edge To this end, with novel technologies has significantly accelerated research process, gradually replacing traditional approach. After screened identified, time-consuming evaluation is another indispensable procedure, especially vivo models. Cellular rodent models have been widely used for whilst non-rodent provide an solution, even potential high-throughput screening. Meanwhile, further molecular mechanisms can elucidate essence underlying activity, which related to several signaling pathways, including Keap1-Nrf2/ARE, mitochondria-dependent apoptosis, TGF-β/SMAD, AMPK/SIRT1/PGC-1α, PI3K/Akt/mTOR, NF-κB. Last but not least, broad manufacture, therapy, cosmetics industry, requires systematic review. This review introduces peptides, categorized new vision. A wide range assays, encompassing cellular models, as well provided comprehensive manner. addition, recent advances analyzed specific cases. Finally, production, systematically reviewed.

Язык: Английский

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Development of novel rivastigmine derivatives as selective BuChE inhibitors for the treatment of AD

Bioorganic Chemistry, Год журнала: 2025, Номер 157, С. 108245 - 108245

Опубликована: Фев. 6, 2025

Язык: Английский

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Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(9), С. 1828 - 1881

Опубликована: Апрель 22, 2024

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a–h), hydrazine monohydrate (NH2NH2•H2O) for regioselective preparation some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a–h). After synthesis characterization mentioned cinnolines (3a–h), in silico multi-targeting inhibitory properties these heterocyclic scaffolds investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, hDHODH, which confirmed their functions roles neurodegenerative (NDs), based on molecular docking studies, obtained results were compared with wide range approved drugs well-known (with IC50, EC50, etc.) compounds. addition, ADMET prediction analysis was performed examine prospective drug synthesized compounds The from studies ADMET-related data demonstrated that series heteroaryl)-5,6-dihydrobenzo[h]cinnolines especially hit ones, can really be turned into potent core new treatment and/or due having reactionable locations, they able further organic reactions (such as cross-coupling reactions), expansion (for example, using other types monohydrates) makes avenue designing novel efficient purpose.

Язык: Английский

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Novel Dibenzoazepine-Substituted Triazole Hybrids as Cholinesterase and Carbonic Anhydrase Inhibitors and Anticancer Agents: Synthesis, Characterization, Biological Evaluation, and In Silico Studies

ACS Omega, Год журнала: 2024, Номер 9(47), С. 46860 - 46878

Опубликована: Ноя. 16, 2024

The new dibenzoazepine-substituted triazole hybrids (12–20) were designed by molecular hybridization approach and synthesized utilizing the Cu(I)-catalyzed click reaction. hybrid structures obtained in high yields (74–98%) with a simple two-step synthesis strategy fully characterized. These compounds assessed for their influence on various metabolic enzymes including human carbonic anhydrase isoenzymes (hCA I hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE). Ki values concerning I, II, AChE, BChE ranges 29.94–121.69, 17.72–89.42, 14.09–44.68, 1.15–48.82 nM, respectively. Compound 13 was 49.70-fold more active than tacrine (standard drug) 5.49-fold AChE. 14 4.16-fold acetazolamide 5.79-fold II. cytotoxic effects of products investigated triple-negative breast cancer cell lines. IC50 most effective calculated between 12.51 ± 1.92 18.07 2.14 μM MDA-MB-231 BT-549 cells. Molecular docking ADME predictions performed. Then, vitro analyzed dynamics (MD) simulation MM/GBSA calculation. Consequently, showed good cytotoxicity inhibition potential colony formation

Язык: Английский

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In Silico Analysis of 9H-(Fluorenyl) Methyl Lysine Carbamate Derivatives as Butyrylcholinesterase Inhibitors

Oriental Journal Of Chemistry, Год журнала: 2025, Номер 40(6), С. 1696 - 1702

Опубликована: Янв. 3, 2025

The successful treatment strategy for Alzheimer's disease focuses on inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to enhance cholinergic activity. This study aimed design fifteen 9H-(fluorenyl)methyl lysine carbamate derivatives (4a-o) as potential BChE inhibitors perform molecular docking studies identify their binding sites evaluate mechanisms the protein by Glide software. results revealed that most potent compounds were 4a, 4c, 4j, with scores of -10.53, -10.57, -10.85 kcal/mol, respectively indicating strong affinities enzyme, suggesting inhibitors. Notably, compound 4j exhibited complete oral absorption, high permeability in MDCK cells, good skin permeability. Its surface area components within acceptable ranges. Thus, is proposed a promising candidate experimental evaluation inhibitor.

Язык: Английский

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Cellulose filter paper immobilized acetylcholinesterase for rapid screening of enzyme inhibitors in Phyllanthus emblica L.

Journal of Pharmaceutical and Biomedical Analysis, Год журнала: 2025, Номер 256, С. 116669 - 116669

Опубликована: Янв. 8, 2025

Язык: Английский

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Rapid screening of acetylcholinesterase inhibitors in Qi-Fu-Yin using magnetic metal–organic frameworks immobilized with acetylcholinesterase

Bioorganic Chemistry, Год журнала: 2025, Номер 156, С. 108183 - 108183

Опубликована: Янв. 17, 2025

Язык: Английский

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Dual inhibition of AChE and MAO-B in Alzheimer’s disease: machine learning approaches and model interpretations

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Язык: Английский

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Pharmacophore-based virtual screening of the chromone derivatives as potential therapeutic for Alzheimer’s disease

Journal of Biomolecular Structure and Dynamics, Год журнала: 2025, Номер unknown, С. 1 - 15

Опубликована: Янв. 28, 2025

Alzheimer's disease is one of the most complex neurological disorders and millions people are suffering from this all over world. In past two decades acetylcholinesterase (AChE) has been explored pathological hallmark. The generation potent AChE inhibitors grown as a rapid tool for efficacious treatment disease. Hence, enzyme extensively drug discovery development therapeutics. We have used chromone derivatives with known biological activities developing Gaussian field-based 3D QSAR pharmacophore model using PHASE module Schrodinger statistically significant R2 Q2 values 0.92 0.9209, respectively. ChEMBL MCULE databases were screened best hypothesis (AAHHRR_4) features hydrogen bond acceptors (A1, A2), hydrophobic regions (H1, H2), aromatic (R1, R2). These subjected to structure-based virtual screening extra precision, MM/GBSA ADME calculations calculating binding free energies pharmacokinetic properties, Subsequently, hit molecules i.e. CHEMBL1319989 MCULE-2246633290 identified. leads exhibited higher docking score (-8.859 -9.984 kcal/mol) ΔGbinding (-57.63 -56.45 compared reference (ΔGbinding= -53.79 kcal/mol). MD simulation study stable interactions energy (ΔGMMPBSA) -27.29 -21.26 kcal/mol MCULE-2246633290, So, generated may be considered valuable AD.

Язык: Английский

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Donepezil-Based Rational Design of N-Substituted Quinazolinthioacetamide Candidates as Potential Acetylcholine Esterase Inhibitors for the Treatment of Alzheimer’s Disease: In vitro and In vivo Studies

RSC Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Donepezil-based rational design of N -substituted quinazoline tethered thioacetamide as potential acetylcholine esterase inhibitors for the treatment Alzheimer's disease.

Язык: Английский

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