Molecular Modeling and Anticholinesterasic Activity of Novel 2-Arylaminocyclohexyl N,N -Dimethylcarbamates

• Published in: Journal of the Brazilian Chemical Society 2013-11, Vol.24 (11), p.1798-1807
• Main Authors: Bagatin, Mariane C., Cândido, Augusto A., Pinheiro, Glaucia M. S., Höehr, Nelci F., Machinski Júnior, Miguel, Mossini, Simone A. G., Basso, Ernani A., Gauze, Gisele F.
• Format: Article
• Language: English
• Subjects: CHEMISTRY, MULTIDISCIPLINARY
• ISSN: 0103-5053; 1678-4790
• DOI: 10.5935/0103-5053.20130225

This work reports a detailed theoretical and experimental study of the novel isomer series cis- and trans-2-arylaminocyclohexyl N,N-dimethylcarbamates as potential inhibitors of cholinesterases. In vitro inhibition assay by Ellman's method with human blood samples showed that the new carbamates are selective to the inhibition of enzyme butyrylcholinesterase (BuChE) with maximum inhibition of 90% and IC50 of 6 and 8 mmol L-1 for the more actives compounds of the series. Molecular modeling studies point to significant differences for the conformations of the compounds in the active sites of enzymes BuChE and acetylcholinesterase (AChE). The results show that the compounds interact more effectively with the active site of enzyme BuChE since the carbamate group is close to the key residues of the catalytic triad.