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Palladium-catalyzed synthesis and anti-AD biological activity evaluation of N-aryl-debenzeyldonepezil analogues.

ABSTRACT: A series of novel N-aryl-debenzeyldonepezil derivatives (1-26) were designed and synthesized as cholinesterase inhibitors by the modification of anti-Alzheimer's disease drug donepezil, using Palladium catalyzed Buchwald-Hartwig cross-coupling reaction as a key chemical synthesis strategy. In vitro cholinesterase inhibition studies demonstrated that the majority of synthesized compounds exhibited high selective inhibition of AChE. Among them, analogue 13 possessing a quinoline functional group showed the most potent AChE inhibition effect and significant neuroprotective effect against H₂O₂-induced injury in SH-SY5Y cells. Furthermore, Compound 13 did not show significant cytotoxicity on SH-SY5Y. These results suggest that 13 is a potential multifunctional active molecule for treating Alzheimer's disease.

SUBMITTER: Xu JJ

PROVIDER: S-EPMC10748399 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Palladium-catalyzed synthesis and anti-AD biological activity evaluation of N-aryl-debenzeyldonepezil analogues.

Xu Jing-Jing JJ Luo Jiao J Xi Heng H Xu Jin-Bu JB Wan Lin-Xi LX

Frontiers in chemistry 20231208

A series of novel N-aryl-debenzeyldonepezil derivatives (1-26) were designed and synthesized as cholinesterase inhibitors by the modification of anti-Alzheimer's disease drug donepezil, using Palladium catalyzed Buchwald-Hartwig cross-coupling reaction as a key chemical synthesis strategy. In vitro cholinesterase inhibition studies demonstrated that the majority of synthesized compounds exhibited high selective inhibition of AChE. Among them, analogue 13 possessing a ...[more]

PMID: 38144888

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