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2000
Volume 21, Issue 7
  • ISSN: 1573-4099
  • E-ISSN: 1875-6697

Abstract

Introduction

Butyrylcholinesterase (BChE) plays a pivotal role in the progression of Alzheimer's disease. Empirical research demonstrated a fundamental alteration in the role of BChE concerning the reduction of cholinergic neurotransmission within the brains of individuals at advanced stages of Alzheimer's.

Methods

This study focuses on developing potent inhibitors for Butyrylcholinesterase (BChE) in the context of Alzheimer's disease (AD) treatment. Building upon previous research, a series of 44 aromatic tertiary amine-based compounds was investigated. Starting with ADME-Tox studies, the pharmacokinetic and pharmacodynamic properties of the compounds were analyzed to select promising candidates for BChE inhibition, which is a crucial factor in AD pathology.

Results

Molecular docking analyses identified compound M18 as the most promising candidate, and further compounds (X9 and X10) were proposed based on M18's chemical structure. These compounds displayed superior properties in terms of binding energies and hydrogen bonds in comparison to M18.

Conclusion

The Molecular Dynamics (MD) simulations, which are over a 500 ns timeframe, confirmed the conformational stability of compounds X9 and X10, compared to M18. Overall, the stated results suggest that the proposed compounds, including X9 and X10 specifically, have a significant potential as candidates for BChE inhibition. This presents a promising avenue for therapeutic intervention in Alzheimer's disease.

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2026-02-01

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Design of New Aromatic Tertiary Amine-based as Butyrylcholinesterase Inhibitors Relying on Molecular Docking, ADME-Tox and Molecular Dynamics
Curr. Computeraided Drug Des. 21, 955 (2025); https://doi.org/10.2174/0115734099302980240722074437
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  • Article Type:     Research Article
Keyword(s): AD pathology; ADME-Tox; aromatic tertiary amine; BChE inhibitors; docking; MD simulation

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