TY - JOUR
T1 - 3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi-Target-Directed Ligands against Alzheimer's Disease
AU - Abdshahzadeh, Helia
AU - Golshani, Mostafa
AU - Nadri, Hamid
AU - Saberi Kia, Iraj
AU - Abdolahi, Zahra
AU - Forootanfar, Hamid
AU - Ameri, Alieh
AU - Tüylü Küçükkılınç, Tuba
AU - Ayazgok, Beyza
AU - Jalili-Baleh, Leili
AU - Sadat Ebrahimi, Seyed Esmaeil
AU - Moghimi, Setareh
AU - Haririan, Ismaeil
AU - Khoobi, Mehdi
AU - Foroumadi, Alireza
N1 - Publisher Copyright:
© 2019 Wiley-VHCA AG, Zurich, Switzerland
PY - 2019/5
Y1 - 2019/5
N2 - 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]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50=0.27 μm). 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 μm and significantly protects PC12 cells from H2O2-damage in a dose-dependent manner.
AB - 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]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50=0.27 μm). 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 μm and significantly protects PC12 cells from H2O2-damage in a dose-dependent manner.
KW - 3-phenylcoumarin
KW - Alzheimer's disease
KW - cholinesterase
KW - neuroprotective activity
KW - synthesis design
KW - β-amyloid
UR - https://www.scopus.com/pages/publications/85064083236
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=performanshacettepe&SrcAuth=WosAPI&KeyUT=WOS:000476956200002&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1002/cbdv.201800436
DO - 10.1002/cbdv.201800436
M3 - Article
C2 - 30957958
AN - SCOPUS:85064083236
SN - 1612-1872
VL - 16
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
IS - 5
M1 - e1800436
ER -