TY - JOUR
T1 - Hetero-annulated coumarins as new AChE/BuChE inhibitors
T2 - synthesis and biological evaluation
AU - Ebrahimi, Seyed Esmaeil Sadat
AU - Ghadirian, Pegah
AU - Emtiazi, Hamideh
AU - Yahya-Meymandi, Azadeh
AU - Saeedi, Mina
AU - Mahdavi, Mohammad
AU - Nadri, Hamid
AU - Moradi, Alireza
AU - Sameem, Bilqees
AU - Vosooghi, Mohsen
AU - Emami, Saeed
AU - Foroumadi, Alireza
AU - Shafiee, Abbas
PY - 2016/9/1
Y1 - 2016/9/1
N2 - A series of chromene-fused coumarins known as 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-diones 4a–o were synthesized through one-pot reaction of appropriate benzaldehydes, dimedone, and 4-hydroxycoumarin in the presence of nano-silica sulfuric acid under solvent-free condition in good yields. The in vitro anticholinesterase assay revealed that the 3-hydroxyphenyl analog 4e showed the highest inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, possessing IC
50 values of 3.28 and 2.19 µM, respectively. The structure-activity relationships study demonstrated that the selectivity for acetylcholinesterase over butyrylcholinesterase could be modulated by introducing second hydroxyl or methoxy substituent on the para-position of the 3-hydroxyphenyl pendent group. The docking study of compound 4e with acetylcholinesterase confirmed π–π stacking interaction between the coumarin moiety and Trp279 as well as the formation of hydrogen bonding between hydroxyl group and Asn85.
AB - A series of chromene-fused coumarins known as 10,11-dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-diones 4a–o were synthesized through one-pot reaction of appropriate benzaldehydes, dimedone, and 4-hydroxycoumarin in the presence of nano-silica sulfuric acid under solvent-free condition in good yields. The in vitro anticholinesterase assay revealed that the 3-hydroxyphenyl analog 4e showed the highest inhibitory activity against both acetylcholinesterase and butyrylcholinesterase, possessing IC
50 values of 3.28 and 2.19 µM, respectively. The structure-activity relationships study demonstrated that the selectivity for acetylcholinesterase over butyrylcholinesterase could be modulated by introducing second hydroxyl or methoxy substituent on the para-position of the 3-hydroxyphenyl pendent group. The docking study of compound 4e with acetylcholinesterase confirmed π–π stacking interaction between the coumarin moiety and Trp279 as well as the formation of hydrogen bonding between hydroxyl group and Asn85.
KW - acetylcholinesterase
KW - Alzheimer’s disease
KW - coumarin-fused derivatives
KW - multicomponent reactions
KW - one-pot synthesis
UR - http://www.scopus.com/inward/record.url?scp=84978164259&partnerID=8YFLogxK
U2 - 10.1007/s00044-016-1626-7
DO - 10.1007/s00044-016-1626-7
M3 - Article
AN - SCOPUS:84978164259
SN - 1054-2523
VL - 25
SP - 1831
EP - 1841
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 9
ER -