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Merck

Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives.

European journal of medicinal chemistry (2014-06-19)
Masoumeh Alipour, Mehdi Khoobi, Alireza Moradi, Hamid Nadri, Farshad Homayouni Moghadam, Saeed Emami, Zeinab Hasanpour, Alireza Foroumadi, Abbas Shafiee
ABSTRACT

A series of 7-hydroxycoumarin derivatives connected by an amidic linker to the different amines were designed and synthesized as cholinesterase inhibitors. Most compounds showed remarkable inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among them, N-(1-benzylpiperidin-4-yl)acetamide derivative 4r with IC50 value of 1.6 μM was the most potent compound against AChE. The selectivity index of compound 4r for anti-AChE activity was about 26. Moreover, the compound 4r significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. The docking study of compound 4r with AChE enzyme showed that both CAS and PAS are occupied by the ligand.

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