Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues

[Image: see text] Palladium/BuAd(2)P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer’s disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridi...

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Autores principales: Wan, Lin-Xi, Miao, Shi-Xing, He, Zhen-Xiang, Li, Xiaohuan, Zhou, Xian-Li, Gao, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444293/
https://www.ncbi.nlm.nih.gov/pubmed/34549134
http://dx.doi.org/10.1021/acsomega.1c03103
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author Wan, Lin-Xi
Miao, Shi-Xing
He, Zhen-Xiang
Li, Xiaohuan
Zhou, Xian-Li
Gao, Feng
author_facet Wan, Lin-Xi
Miao, Shi-Xing
He, Zhen-Xiang
Li, Xiaohuan
Zhou, Xian-Li
Gao, Feng
author_sort Wan, Lin-Xi
collection PubMed
description [Image: see text] Palladium/BuAd(2)P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer’s disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H(2)O(2)-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE).
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spelling pubmed-84442932021-09-20 Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues Wan, Lin-Xi Miao, Shi-Xing He, Zhen-Xiang Li, Xiaohuan Zhou, Xian-Li Gao, Feng ACS Omega [Image: see text] Palladium/BuAd(2)P efficiently catalyzed the direct α-arylation of ketone in the anti-Alzheimer’s disease drug donepezil, leading to 15 aryldonepezil analogues exhibiting high selective inhibition of acetylcholinesterase (AChE). The cell-based assays revealed that the 3-methylpridinyl analogue (12) shows significantly lower toxicity compared to donepezil and remarkable neuroprotective activity against H(2)O(2)-induced damage in SH-SY5Y cells. Docking results of compound 12 also interpreted the possible mechanism of the selective inhibition between AChE and butyrylcholinesterase (BuChE). American Chemical Society 2021-09-01 /pmc/articles/PMC8444293/ /pubmed/34549134 http://dx.doi.org/10.1021/acsomega.1c03103 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Wan, Lin-Xi
Miao, Shi-Xing
He, Zhen-Xiang
Li, Xiaohuan
Zhou, Xian-Li
Gao, Feng
Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title_full Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title_fullStr Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title_full_unstemmed Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title_short Pd-Catalyzed Direct Modification of an Anti-Alzheimer’s Disease Drug: Synthesis and Biological Evaluation of α-Aryl Donepezil Analogues
title_sort pd-catalyzed direct modification of an anti-alzheimer’s disease drug: synthesis and biological evaluation of α-aryl donepezil analogues
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444293/
https://www.ncbi.nlm.nih.gov/pubmed/34549134
http://dx.doi.org/10.1021/acsomega.1c03103
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