title: Acetylcholinesterase-inhibiting activity of salicylanilide N-alkylcarbamates and their molecular docking.
abstract: A series of twenty-five novel salicylanilide N-alkylcarbamates were investigated as potential acetylcholinesterase inhibitors. The compounds were tested for their ability to inhibit acetylcholinesterase (AChE) from electric eel (Electrophorus electricus L.). Experimental lipophilicity was determined, and the structure-activity relationships are discussed. The mode of binding in the active site of AChE was investigated by molecular docking. All the discussed compounds expressed significantly higher AChE inhibitory activity than rivastigmine and slightly lower than galanthamine. Disubstitution by chlorine in C'(₃,₄) of the aniline ring and the optimal length of hexyl-undecyl alkyl chains in the carbamate moiety provided the most active AChE inhibitors. Monochlorination in C'(₄) exhibited slightly more effective AChE inhibitors than in C'(₃). Generally it can be stated that compounds with higher lipophilicity showed higher inhibition, and the activity of the compounds is strongly dependent on the length of the N-alkyl chain.
authors.affiliation: Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 53210 Pardubice, Czech Republic. ales.imramovsky@upce.cz
authors.forename: Ales
authors.initials: A
authors.lastname: Imramovsky
authors.forename: Sarka
authors.initials: S
authors.lastname: Stepankova
authors.forename: Jan
authors.initials: J
authors.lastname: Vanco
authors.forename: Karel
authors.initials: K
authors.lastname: Pauk
authors.forename: Juana
authors.initials: J
authors.lastname: Monreal-Ferriz
authors.forename: Jarmila
authors.initials: J
authors.lastname: Vinsova
authors.forename: Josef
authors.initials: J
authors.lastname: Jampilek
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002219:Carbamates / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004593:Electrophorus / Q000378:metabolism; D005702:Galantamine / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D048448:Phenylcarbamates / Q000378:metabolism; D000068836:Rivastigmine; D012458:Salicylanilides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002219:Carbamates; D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D012458:Salicylanilides; D005702:Galantamine; D000110:Acetylcholinesterase; C034596:salicylanilide; D000068836:Rivastigmine