AUTHOR=Xu Jing-Jing , Luo Jiao , Xi Heng , Xu Jin-Bu , Wan Lin-Xi 

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

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2023.1282978

DOI=10.3389/fchem.2023.1282978

ISSN=2296-2646

ABSTRACT=A series of novel N-aryl-debenzeyldonepezil derivatives (1-26) were designed and synthesized as cholinesterases 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 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.