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Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD....

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Autores principales: Zhou, Yi, He, Ying, Teng, Xue, Mi, Jing, Yang, Jing, Wei, Rongrui, Liu, Wenmin, Ma, Qinge, Tan, Zhenghuai, Sang, Zhipei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327518/
https://www.ncbi.nlm.nih.gov/pubmed/37414563
http://dx.doi.org/10.1080/14756366.2023.2231661
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author Zhou, Yi
He, Ying
Teng, Xue
Mi, Jing
Yang, Jing
Wei, Rongrui
Liu, Wenmin
Ma, Qinge
Tan, Zhenghuai
Sang, Zhipei
author_facet Zhou, Yi
He, Ying
Teng, Xue
Mi, Jing
Yang, Jing
Wei, Rongrui
Liu, Wenmin
Ma, Qinge
Tan, Zhenghuai
Sang, Zhipei
author_sort Zhou, Yi
collection PubMed
description Alzheimer’s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid–donepezil–rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC(50) = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD.
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spelling pubmed-103275182023-07-08 Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease Zhou, Yi He, Ying Teng, Xue Mi, Jing Yang, Jing Wei, Rongrui Liu, Wenmin Ma, Qinge Tan, Zhenghuai Sang, Zhipei J Enzyme Inhib Med Chem Research Paper Alzheimer’s disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid–donepezil–rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC(50) = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD. Taylor & Francis 2023-07-06 /pmc/articles/PMC10327518/ /pubmed/37414563 http://dx.doi.org/10.1080/14756366.2023.2231661 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
spellingShingle Research Paper
Zhou, Yi
He, Ying
Teng, Xue
Mi, Jing
Yang, Jing
Wei, Rongrui
Liu, Wenmin
Ma, Qinge
Tan, Zhenghuai
Sang, Zhipei
Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title_full Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title_fullStr Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title_full_unstemmed Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title_short Development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer’s disease
title_sort development of novel salicylic acid–donepezil–rivastigmine hybrids as multifunctional agents for the treatment of alzheimer’s disease
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327518/
https://www.ncbi.nlm.nih.gov/pubmed/37414563
http://dx.doi.org/10.1080/14756366.2023.2231661
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