title: Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3',4':5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase.
abstract: Novel hybrid derivatives of two known scaffolds; tetrahydroaminoquinoline and coumarin were synthesized and evaluated for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. By means of an efficient nanocatalyst, the reaction time for the syntheses of the target compounds was reduced. Subsequently, Ellman's modified method was used to evaluate the enzyme inhibitory activity of the synthesized structures. It was observed that most hybrid structures were moderate to potent inhibitors of AChE compared to Tacrine as the reference drug among which 7f with 4-fluorophenyl substituent was the most active compound (IC50=5 nM).
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoobi
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Alipour
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.forename: Seyyede Faeze
authors.initials: SF
authors.lastname: Razavi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghandi
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001578:Benzopyrans; D002800:Cholinesterase Inhibitors; D003374:Coumarins; D013619:Tacrine; C030123:coumarin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Alzheimer's disease; Cholinesterase inhibitor; Coumarin; Docking study; Tacrine