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Molecules 2012, 17(9), 10142-10158; doi:10.3390/molecules170910142
Article

Acetylcholinesterase-Inhibiting Activity of Salicylanilide N-Alkylcarbamates and Their Molecular Docking

1,* , 2, 3, 1, 4, 4 and 3,*
1 Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic 2 Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic 3 Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho 1/3, 612 42 Brno, Czech Republic 4 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic
* Authors to whom correspondence should be addressed.
Received: 30 July 2012 / Revised: 1 August 2012 / Accepted: 10 August 2012 / Published: 24 August 2012
(This article belongs to the Section Medicinal Chemistry)
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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.
Keywords: 4-chloro-2-(chlorophenylcarbamoyl)phenyl alkylcarbamates; in vitro acetyl-cholinesterase inhibition; lipophilicity; molecular docking 4-chloro-2-(chlorophenylcarbamoyl)phenyl alkylcarbamates; in vitro acetyl-cholinesterase inhibition; lipophilicity; molecular docking
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Imramovsky, A.; Stepankova, S.; Vanco, J.; Pauk, K.; Monreal-Ferriz, J.; Vinsova, J.; Jampilek, J. Acetylcholinesterase-Inhibiting Activity of Salicylanilide N-Alkylcarbamates and Their Molecular Docking. Molecules 2012, 17, 10142-10158.

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