A Novel Galantamine–Curcumin Hybrid Inhibits Butyrylcholinesterase: A Molecular Dynamics Study DOI Creative Commons

Evdokiya Salamanova,

Mariyana Atanasova, Irini Doytchinova

et al.

Chemistry, Journal Year: 2024, Volume and Issue: 6(6), P. 1645 - 1657

Published: Dec. 16, 2024

Cholinesterases are enzymes that break down the neurotransmitter acetylcholine in nervous system. The two main types acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). AChE inhibitors used to treat Alzheimer’s disease by increasing levels. BChE activity increases later stages of Alzheimer’s, suggesting it might contribute disease. In previous experiments, was found a newly designed hybrid galantamine (GAL) curcumin (CCN) (compound 4b) decreases murine brain homogenates. Here, we explore this observation using molecular dynamics simulations. GAL CCN were also studied for comparison. structures complexes between ligands predicted docking. Then, simulations performed evaluate stability interactions enzyme over simulated time 1 μs. All three formed stable with BChE. Compound 4b more hydrogen bonds other compared CCN, stronger binding affinity. explain its superior anti-BChE observed experiments.

Language: Английский

Design and synthesis of new 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives: selective butyrylcholinesterase inhibitors against Alzheimer’s disease DOI Creative Commons
Aida Iraji, Roshanak Hariri, Mohammad Hashem Hashempur

et al.

BMC Chemistry, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 15, 2025

Alzheimer's disease (AD) remains a significant public health challenge due to its progressive cognitive impairment and the absence of proven treatments. In this study, several novel 1,2,3-triazole-methoxyphenyl-1,3,4-oxadiazole derivatives were synthesized evaluated for their ability inhibit key enzymes associated with AD: acetylcholinesterase (AChE) butyrylcholinesterase (BChE). Structure-activity relationship (SAR) analysis revealed that featuring electron-withdrawing groups, particularly nitro fluorine substituents, exhibited remarkable inhibitory activity against BChE while showing minimal effectiveness AChE. Among these, compound 13s (R = 4-CH3, R' 4-NO2) demonstrated highest potency, selectively targeting an IC50 value 11.01 µM. Molecular docking molecular dynamics (MD) simulations provided deeper insights into favorable interactions between these compounds BChE. Additionally, cytotoxicity studies confirmed active compound's limited toxicity toward normal cells, indicating promising therapeutic profile. These findings suggest selective anti-BChE hold potential consideration in later stages AD treatment.

Language: Английский

Citations

0
Naphthyl-functionalized acetamide derivatives: Promising agents for cholinesterase inhibition and antioxidant therapy in Alzheimer’s disease DOI
Lorena Camargo-Ayala, Luis Prent-Peñaloza, Edison Osorio

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107896 - 107896

Published: Oct. 20, 2024

Language: Английский

Citations

3
Design, Synthesis, and Bio-Evaluation of C2-Aryl Galantamine Derivatives DOI
Shuishu Wang,

Wan-Sheng Ji,

Lianhai Shan

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Virtual screening and molecular dynamics of anti-Alzheimer compounds from Cardiospermum halicacabum via GC-MS DOI Creative Commons

Selvan Kaviyarasu,

Nallamuthu Padmanaban,

Sulekha Khute

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 4, 2025

Background Ayurveda is an ancient Indian medicinal system that uses plants for their neuroprotective effects. claims the ( C. halicacabum ) leaves possess significant properties. Alzheimer’s characterized by accumulation of amyloid-β, acetylcholinesterase, and tau tangles interfere with neural transmission impair cognitive abilities. Objectives This study aimed to identify novel potential anti-Alzheimer phytoconstituents using in silico methods. Methods utilized Box–Behnken design within response surface methodology (RSM) optimize combine effects process variables, namely powder weight, solvent volume, extraction time, on microwave-assisted (MAE) leaves. The optimization revealed these along microwave usage, significantly influenced yield. ethanolic extract was examined gas chromatography-mass spectrometry (GC–MS) analysis, identified were further analyzed through computer-based simulations, including docking, absorption, distribution, metabolism, excretion, toxicity (ADMET) studies, assessment drug-likeness, molecular dynamics, LigPlot density functional theory (DFT) analysis. Results Gas (GC-MS) analysis 40 37 successfully characterized. Molecular docking dynamics simulations two lead compounds, acetic acid (dodecahydro-7-hydroxy-1,4b,8,8-tetramethyl-10-oxo-2(1H)-phenanthrenylidene)-,2-(dimethylamino)ethyl ester, [1R-(1. alpha)], 1-(2-hydroxyethoxy)-2-methyldodecane, which exhibited superior stability docked complex compared galantamine. Conclusion Based computational predictions observed pharmacological properties, findings suggest may have therapeutic against selected AD targets.

Language: Английский

Citations

0
A Bright Future for Photopharmaceuticals Addressing Central Nervous System Disorders: State of the Art and Challenges Toward Clinical Translation DOI
Rudolf L. Z. Ganzoni, Sofie S. Bournons, Erick M. Carreira

et al.

Medicinal Research Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

ABSTRACT Photopharmacology is an innovative approach that uses light to activate drugs. This method offers the potential for highly localized and precise drug activation, making it particularly promising treatment of neurological disorders. Despite enticing prospects photopharmacology, its application treat human central nervous system (CNS) diseases remains be demonstrated. In this review, we provide overview prominent strategies design activation photopharmaceutical agents in field neuroscience. Photocaged photoswitchable drugs bioactive molecules are discussed, instructive list examples provided highlight compound strategies. Special emphasis placed on photoactivatable compounds modulation glutamatergic, GABAergic, dopaminergic, serotonergic neurotransmission conditions, as well various photoresponsive with improved pain management. Compounds holding promise clinical translation discussed in‐depth their future applications assessed. Neurophotopharmaceuticals have yet achieve breakthrough clinic, both delivery not reached full maturity. However, by describing current state art providing illustrative case studies, offer a perspective opportunities neurophotopharmacology focused addressing CNS

Language: Английский

Citations

0
Design, synthesis, and bio-evaluation of C1-aryl galantamine derivatives DOI
Shuishu Wang,

Wan-Sheng Ji,

Longjiang Chen

et al.

Fitoterapia, Journal Year: 2025, Volume and Issue: 183, P. 106535 - 106535

Published: April 9, 2025

Language: Английский

Citations

0
Design, synthesis and evaluation of novel L-tryptophan derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, anti-inflammatory, antioxidant and neuroprotection properties against Alzheimer's disease DOI
Haiyang Yu, Yinfang Chen, Huizhen Li

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 161, P. 108478 - 108478

Published: April 17, 2025

Language: Английский

Citations

0
Dual inhibitors of butyrylcholinesterase and histone deacetylase 6 for the treatment of Alzheimer’s disease: design, synthesis, and biological evaluation DOI
Bingbing Lv,

Zhenqi Wang,

Qinjie Wang

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 127, P. 118219 - 118219

Published: May 1, 2025

Language: Английский

Citations

0
Discovery, Biological Evaluation and Binding Mode Investigation of Novel Butyrylcholinesterase Inhibitors Through Hybrid Virtual Screening DOI Creative Commons
Lizi Li,

Puchen Zhao,

Can Yang

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(10), P. 2093 - 2093

Published: May 8, 2025

Butyrylcholinesterase (BChE), plays a critical role in alleviating the symptoms of Alzheimer’s disease (AD) by regulating acetylcholine levels, emerging as an attractive target for AD treatment. This study employed quantitative structure–activity relationship (QSAR) model based on ECFP4 molecular fingerprints with several machine learning algorithms (XGBoost, RF, SVM, KNN), among which XGBoost showed best performance (AUC = 0.9740). A hybrid strategy integrating ligand- and structure-based virtual screening identified 12 hits from Topscience core database, three were first time. Among them, piboserod Rotigotine demonstrated BChE inhibitory potency (IC50 15.33 μM 12.76 μM, respectively) exhibited favorable safety profiles well neuroprotective effects vitro. Notably, Rotigotine, marketed drug, was newly recognized its anti-AD potential, further enzyme kinetic analyses revealing that it acts mixed-type inhibitor non-competitive mode. Fluorescence spectroscopy, docking, dynamics simulations clarified their binding modes stability. provides innovative discovery inhibitors, not only identifies promising drug candidates treatment but also demonstrates potential discovery.

Language: Английский

Citations

0
Pharmacokinetics and fate of free and encapsulated IRD800CW-labelled human BChE intravenously administered in mice DOI
Tatiana N. Pashirova, Zukhra Shaihutdinova, D. A. Tatarinov

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 282, P. 137305 - 137305

Published: Nov. 7, 2024

Language: Английский

Citations

1