TY - JOUR
T1 - Design and synthesis of novel coumarin-pyridinium hybrids
T2 - in vitro cholinesterase inhibitory activity
AU - Vafadarnejad, Fahimeh
AU - Mahdavi, Mohammad
AU - Karimpour-Razkenari, Elahe
AU - Edraki, Najmeh
AU - Sameem, Bilqees
AU - Khanavi, Mahnaz
AU - Saeedi, Mina
AU - Akbarzadeh, Tahmineh
PY - 2018/4
Y1 - 2018/4
N2 - A novel series of coumarin-pyridinium hybrids were synthesized and evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's method. Among synthesized compounds, 1-(3-fluorobenzyl)-4-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7l) was found to be the most active compound toward AChE (IC50 = 10.14 µM), 1-(3-chlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7g) and 1-(2,3-dichlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium chloride (7h) depicted the best BChE inhibitory activity (IC50s = 0.32 and 0.43 µM, respectively). Although most compounds showed moderate to good anti-AChE activity, their anti-BChE activity was more significant and compound 7g was found as the most selective BChE with SI of 101.18. Also, kinetic study of the compounds 7g and 7l displayed a mixed type inhibition for both AChE and BChE. Furthermore, they were evaluated against β-secretase; however, they showed low inhibitory activity.
AB - A novel series of coumarin-pyridinium hybrids were synthesized and evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's method. Among synthesized compounds, 1-(3-fluorobenzyl)-4-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7l) was found to be the most active compound toward AChE (IC50 = 10.14 µM), 1-(3-chlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7g) and 1-(2,3-dichlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium chloride (7h) depicted the best BChE inhibitory activity (IC50s = 0.32 and 0.43 µM, respectively). Although most compounds showed moderate to good anti-AChE activity, their anti-BChE activity was more significant and compound 7g was found as the most selective BChE with SI of 101.18. Also, kinetic study of the compounds 7g and 7l displayed a mixed type inhibition for both AChE and BChE. Furthermore, they were evaluated against β-secretase; however, they showed low inhibitory activity.
KW - Cholinesterases
KW - Coumarins
KW - Docking study
KW - Kinetic study
KW - Pyridinium salts
KW - β-secretase (BACE1)
UR - http://www.scopus.com/inward/record.url?scp=85041641811&partnerID=8YFLogxK
U2 - 10.1016/j.bioorg.2018.01.013
DO - 10.1016/j.bioorg.2018.01.013
M3 - Article
C2 - 29421707
AN - SCOPUS:85041641811
VL - 77
SP - 311
EP - 319
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
SN - 0045-2068
ER -