A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl- and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl- compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure⁻activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host⁻target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.

Department of Biological and Biochemical Sciences Faculty of Chemical Technology University of Pardubice Studentska 573 532 10 Pardubice Czech Republic

Department of Bioorganic Chemistry Faculty of Chemistry Wrocław University of Science and Technology Wyb Wyspiańskiego 27 50 370 Wrocław Poland

Department of Energy Saving and Air Protection Central Mining Institute Plac Gwarkow 1 40 166 Katowice Poland

Division of Biologically Active Complexes and Molecular Magnets Regional Centre of Advanced Technologies and Materials Faculty of Science Palacky University Slechtitelu 27 78371 Olomouc Czech Republic

Institute of Chemistry University of Silesia Szkolna 9 40 007 Katowice Poland

Institute of Neuroimmunology Slovak Academy of Sciences Dubravska cesta 9 84510 Bratislava Slovakia

Institute of Organic Chemistry and Technology Faculty of Chemical Technology University of Pardubice Studentska 573 532 10 Pardubice Czech Republic

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