Neurobehavioral investigation and acetylcholinesterase inhibitory activity study for some new coumarin derivatives
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Date
2019
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Elsevier Masson SAS
Series Info
European Journal of Medicinal Chemistry
182
182
Scientific Journal Rankings
Abstract
Twenty four 6-aminocoumarin based derivatives were synthesized according to two schemes. All the compounds were screened for their acetylcholinesterase inhibitory activity where compound 5b proved to be the most potent AChE inhibitor with (IC50 = 37 nM) compared to tacrine and donepezil (IC50 = 55.0 and 59.0 nM, respectively). Six compounds 2f, 2g, 4b, 5b, 8b and 9b revealed superior activity over donepezil and a conclusive structure activity relationship study was conducted explaining the obtained results. Furthermore, compounds 2f, 4b and 5b were investigated for their neurobehavioral effect in vivo. All the tested compounds showed improvement of neurobehavioral experiments using donepezil as reference drug. In addition, compounds 2f, 4b and 5b were able to reduce extracellular deposition of amyloid beta 42 in a comparable manner to donepezil. The binding modes of the synthesized compounds were evaluated in silico via molecular docking in the active site of AChE, as well as molecular dynamics simulation study. A pharmacophore model was generated for the newly synthesized compounds. � 2019 Elsevier Masson SAS
Description
Scopus
Keywords
Acetylcholinesterase inhibitors, Alzheimer's disease, Coumarin derivatives, 2 (4 fluorophenyl) 3 (2 oxo 2h chromen 6 yl)thiazolidin 4 one, 2 (4 methoxyphenyl) 3 (2 oxo 2h chromen 6 yl)thiazolidin 4 one, 2 [(2 oxo 2h chromen 6 yl)amino] n phenylacetamide, 2 [4 (methylthio)phenyl] 3 (2 oxo 2h chromen 6 yl)thiazolidin 4 one, 5 (4 bromrobenzylidene) 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 (4 chlorobenzylidene) 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 (4 fluorobenzylidene) 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 (4 methoxybenzylidene) 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 benzylidene 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 [4 (dimethylamino)benzylidene] 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 5 [4 (methylthio)benzylidene] 2 [(2 oxo 2h chromen 6 yl)imino]thiazolidin 4 one, 6 (benzylideneamino) 2h chromen 2 one, 6 [(2 morpholino 2 oxoethyl)amino] 2h chromen 2 one, 6 [(2 oxo 2 phenylethyl)amino] 2h chromen 2 one, 6 [(4 bromobenzylidene)amino] 2h chromen 2 one, 6 [(4 chlorobenzylidene)amino] 2h chromen 2 on, 6 [(4 flurobenzylidene)amino] 2h chromen 2 one, 6 [(4 methoxybenzylidene)amino] 2h chromen 2 one, 6 [[2 (4 methoxyphenyl) 2 oxo ethyl]amino) 2h chromen 2 one, 6 [[2 oxo 2 (4 phenylpiperazin 1 yl)ethyl]amino] 2h chromen 2 one, 6 [[4 (dimethylamino)benzylidene]amino] 2h chromen 2 one, 6 [[4 (methylthio)benzylidene]amino] 2h chromen 2 one, acetylcholinesterase, cholinesterase inhibitor, coumarin derivative, donepezil, n (4 fluorophenyl) 2 [(2 oxo 2h chromen 6 yl)amino]acetamide, n (4 methoxyphenyl) 2 [(2 oxo 2h chromen 6 yl)amino]acetamide, nootropic agent, tacrine, unclassified drug, acetylcholinesterase, cholinesterase inhibitor, coumarin derivative, adult, Alzheimer disease, animal experiment, animal model, animal tissue, Article, cognition, computer model, controlled study, drug synthesis, enzyme activity, enzyme inhibition, escape latency, IC50, in vivo study, male, memory consolidation, molecular docking, molecular dynamics, Morris water maze test, mouse, nonhuman, novel object recognition test, pharmacophore, spatial memory, structure activity relation, Y-maze test, animal, chemical structure, chemistry, dose response, metabolism, synthesis, Acetylcholinesterase, Animals, Cholinesterase Inhibitors, Coumarins, Dose-Response Relationship, Drug, Male, Mice, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship