Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases

Neurology International, Год журнала: 2025, Номер 17(2), С. 26 - 26

Опубликована: Фев. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Язык: Английский

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Essential oils of Plumeria alba L. and Plumeria rubra L. growing in Egypt: GC/MS analysis, molecular dynamics and in-vitro anti-cholinesterase activity

Industrial Crops and Products, Год журнала: 2024, Номер 221, С. 119316 - 119316

Опубликована: Авг. 3, 2024

Язык: Английский

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Assessing indole derivative molecules as dual acetylcholinesterase and butyrylcholinesterase inhibitors through In Vitro inhibition and molecular modelling studies

Journal of Molecular Structure, Год журнала: 2024, Номер 1311, С. 138276 - 138276

Опубликована: Апрель 10, 2024

Язык: Английский

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Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction

Pathology - Research and Practice, Год журнала: 2023, Номер 251, С. 154856 - 154856

Опубликована: Окт. 5, 2023

Язык: Английский

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Untargeted urine metabolomics reveals dynamic metabolic differences and key biomarkers across different stages of Alzheimer’s disease

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Янв. 27, 2025

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, with mild cognitive impairment (MCI) often serving as its precursor stage. Early intervention at the MCI stage can significantly delay AD onset. Methods This study employed untargeted urine metabolomics, data obtained from MetaboLights database (MTBLS8662), combined orthogonal partial least squares-discriminant analysis (OPLS-DA) to examine metabolic differences across different stages of progression. A decision tree approach was used identify key metabolites within enriched pathways. These were then utilized construct and validate an progression prediction model. Results The OPLS-DA model effectively distinguished characteristics stages. Pathway enrichment revealed that Drug metabolism all stages, while Retinol particularly prominent during transition Key such Theophylline, Vanillylmandelic Acid (VMA), Adenosine showed significant differencesdifferencesin early disease, whereas 1,7-Dimethyluric Acid, Cystathionine, Indole exhibited strong predictive value transition. play crucial role in monitoring Predictive models based on these demonstrated excellent classification capabilities. Conclusion systematically analyzed dynamic identified pathways potential biomarkers for intervention. Utilizing urinary findings provide theoretical basis contribute improving prevention strategies, thereby potentially delaying

Язык: Английский

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Exploration of 1,3,4‐oxadiazoles Engrafted With Indole and Phthalimide Scaffolds as Multi Target Peroxidase, Acetylcholinesterase, and Butyrylchloinesterase Inhibitors: Synthesis, DFT Calculations, and Molecular Docking Studies

ChemistrySelect, Год журнала: 2025, Номер 10(6)

Опубликована: Фев. 1, 2025

Abstract Here, we present the structural and pharmacological characteristics of 2‐(4‐(5‐(3,5‐disubstituted‐1 H ‐indol‐2‐yl)‐1,3,4‐oxadiazol‐2‐yl)phenyl)isoindoline‐1,3‐diones 5(a‐h) as a strong antioxidant anti‐Alzheimer's disease activity using synergistic combination theoretical experimental techniques. The structures novel compounds were analyzed by spectral analysis (IR, NMR Mass spectrometry). DFT calculations for selected applying B3LYP hybrid functional 6–31G (d, p) basis set. predictions regarding ADMET properties, drug‐likeness, toxicity, including favorable bioavailability all synthesized disclosed. All newly 5(a–h) illustrated well to comparable inhibitory potentials ranging from IC 50 values 12.12 ± 0.02 µM 36.31 0.26 µM, 04.08 0.86 12.42 0.32 08.05 0.06 26.36 0.52 against peroxidase , acetylcholinesterase (AChE) butyrylcholinesterase (BChE) respectively. Amongst, compound 5a showed excellent with 0.86, peroxidase, Finally, aforesaid taken in silico molecular modeling cytochrome c (PDB id: 2 × 08), ID: 7E3H), 4BDS).

Язык: Английский

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Dual inhibition of canonical and noncanonical PAR‐1 by SCH79797 mitigates neurodegeneration in 3‐NP‐induced Huntington's disease: An in vivo and in silico approach

Archiv der Pharmazie, Год журнала: 2025, Номер 358(3)

Опубликована: Март 1, 2025

Abstract Though abnormal platelet function is detected in Huntington's disease (HD), thrombin's role indistinct. Through protease‐activated receptor 1 (PAR‐1) activation, thrombin triggers intricate pathways relevant to HD. Therefore, we propose that posttreatment with the PAR‐1 inhibitor SCH79797 may alleviate symptoms a 3‐nitropropionic acid (3‐NP) HD model. Wistar rats were administered 3‐NP alone or treated SCH79797. In silico study showed better blood–brain barrier (BBB) diffusion by than vorapaxar. Docking blocks thrombin/PAR‐1 binding and directly inhibits metalloproteinase (MMP)‐1. Molecular dynamics confirmed minimal energy deviation stable interactions both MMP‐1 root mean square (RMSD) verified conformational stability. vivo part, behavioral striatal improvements observed, reducing levels of MMP‐1, expression PAR‐1, N ‐methyl‐ d ‐aspartate (NMDA) subunits (1 2B), MMP‐9, while increasing claudin‐5, contributing BBB integrity. also lowered tumor necrosis factor (TNF)‐α mitofusin (Mfn)‐2, rebalanced redox system malondialdehyde (MDA) enhancing superoxide dismutase (SOD), prevented 3‐NP‐induced mitophagy via PTEN‐induced kinase (PINK)‐1/ubiquitin pathway. inhibited apoptosis, caspase‐3 cytochrome C, increased voltage‐dependent anion channel‐1 (VDAC1) maintain mitochondrial function. Overall, canonically noncanonically counter excitotoxicity, oxidative stress, inflammation, mitophagy, thereby preserving integrity, improving histological outcomes, performance.

Язык: Английский

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Machine learning tools for the characterization of bioactive metabolites derived from different parts of Ochrosia elliptica Labill. for the management of Alzheimer's disease

RSC Advances, Год журнала: 2025, Номер 15(14), С. 10671 - 10690

Опубликована: Янв. 1, 2025

Ochroisa elliptica revealed 41 compounds using UPLC-MS/MS and assessed their binding affinities to cholinesterase enzymes through molecular docking. A quercetin derivative exhibited the strongest binding. Additionally, dynamic simulations confirmed stable interactions.

Язык: Английский

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Design of vilazodone-donepezil chimeric derivatives as acetylcholinesterase inhibitors by QSAR, molecular docking and molecular dynamics simulations

Physical Chemistry Chemical Physics, Год журнала: 2024, Номер 26(26), С. 18149 - 18161

Опубликована: Янв. 1, 2024

Alzheimer's disease (AD) is a that affects the cognitive abilities of older adults, and it one biggest global medical challenges 21st century. Acetylcholinesterase (AChE) can increase acetylcholine concentrations improve function in patients, potential target to develop small molecule inhibitors for treatment (AD). In this study, 29 vilazodone-donepezil chimeric derivatives are systematically studied using 3D-QSAR modeling, robust reliable Topomer CoMFA model was obtained with:

Язык: Английский

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Metabolomic Profiling of Barley Extracts Obtained via Different Solvents and Evaluation of Their Anti-Inflammatory Efficacy

Food Bioscience, Год журнала: 2024, Номер 61, С. 104682 - 104682

Опубликована: Июль 6, 2024

Язык: Английский

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