Recent Advances in The Therapeutic Insights of Thiazole Scaffolds as Acetylcholinesterase Inhibitors

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117331 - 117331

Published: Jan. 1, 2025

Language: Английский

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Structural Bioinformatics Applied to Acetylcholinesterase Enzyme Inhibition

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3781 - 3781

Published: April 17, 2025

Acetylcholinesterase (AChE) is a critical enzyme involved in neurotransmission by hydrolyzing acetylcholine at the synaptic cleft, making it key target for drug discovery, particularly treatment of neurodegenerative disorders such as Alzheimer’s disease. Computational approaches, molecular docking and dynamics (MD) simulations, have become indispensable tools identifying optimizing AChE inhibitors predicting ligand-binding affinities, interaction mechanisms, conformational dynamics. This review serves comprehensive guide future research on using MD simulations. It compiles analyzes studies conducted over past five years, providing evaluation most widely used computational tools, including AutoDock, AutoDock Vina, GROMACS, which significantly contributed to advancement inhibitor screening. Furthermore, we identify PDB ID: 4EY7, frequently crystal structure studies, highlight Donepezil, well-established reference molecule employed control screening novel inhibitors. By examining these aspects, this aims enhance accuracy reliability virtual approaches researchers selecting appropriate methodologies. The integration simulations not only improves hit identification lead optimization but also provides deeper mechanistic insights into AChE–ligand interactions, contributing rational design more effective

Language: Английский

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Functionalized Thiadiazole: Synthesis, insecticidal activity, molecular docking and DFT studies of some new 5-substituted 1,2,4-Thiadiazoles based on Norfloxacin

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 161, P. 108510 - 108510

Published: April 29, 2025

Language: Английский

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Assessing the Potential of 1,2,3-Triazole-Dihydropyrimidinone Hybrids against Cholinesterases: In Silico, In Vitro, and In Vivo Studies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11153 - 11153

Published: Oct. 17, 2024

Combining the pharmacological properties of 1,2,3-triazole and dihydropyrimidinone classes compounds, two small families mono- di(1,2,3-triazole)-dihydropyrimidinone hybrids, A B, were previously synthesized. The main objective this work was to investigate potential anti-Alzheimer effects these hybrids. inhibitory activities cholinesterases (AChE BuChE), antioxidant activity, mechanism through in silico (molecular docking) solution (STD-NMR) experiments evaluated. 1,2,3-triazole-dihydropyrimidinone hybrids (A B) showed moderate vitro activity on eqBuChE (IC50 values between 1 58.4 μM). best inhibitor hybrid B4, featuring cores, which exhibited stronger inhibition than galantamine, with an IC50 ± 0.1 μM for eqBuChE, a mixed mechanism. Among A, most promising A1, exhibiting 12 2 µM, similar that galantamine. Molecular docking STD-NMR revealed key binding interactions inhibitors BuChE. Hybrids B did not display Artemia salina toxicity below 100 μM.

Language: Английский

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