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3‐Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi‐Target‐Directed Ligands against Alzheimer's Disease
Author(s) -
Abdshahzadeh Helia,
Golshani Mostafa,
Nadri Hamid,
Saberi Kia Iraj,
Abdolahi Zahra,
Forootanfar Hamid,
Ameri Alieh,
Tüylü Küçükkılınç Tuba,
Ayazgok Beyza,
JaliliBaleh Leili,
Sadat Ebrahimi Seyed Esmaeil,
Moghimi Setareh,
Haririan Ismaeil,
Khoobi Mehdi,
Foroumadi Alireza
Publication year - 2019
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201800436
Subject(s) - chemistry , butyrylcholinesterase , coumarin , moiety , acetylcholinesterase , linker , aryl , aché , amine gas treating , stereochemistry , combinatorial chemistry , enzyme , biochemistry , organic chemistry , alkyl , computer science , operating system
Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross‐linker are investigated in acetyl‐ and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3‐(3,4‐Dichlorophenyl)‐7‐[4‐(diethylamino)butoxy]‐2 H ‐chromen‐2‐one ( 4y ) is identified as the most potent compound against AChE (IC 50 =0.27 μ m ). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed‐type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks β‐amyloid (Aβ) self‐aggregation with a ratio of 44.11 % at 100 μ m and significantly protects PC12 cells from H 2 O 2 ‐damage in a dose‐dependent manner.