Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling

• Published in: Journal of the Brazilian Chemical Society Vol. 27; no. 9; pp. 1616 - 1625
• Main Authors: Yamazaki, Diego A. S., Candido, Augusto A., Bagatin, Mariane C., Machinski, Miguel, Mossini, Simone A. G., Pontes, Rodrigo M., Rosa, Fernanda A., Basso, Ernani A., Gauze, Gisele F.
• Format: Journal Article
• Language: English
• Published: SAO PAULO Soc Brasileira Quimica 01.09.2016; Sociedade Brasileira de Química
• Subjects: Chemistry; CHEMISTRY, MULTIDISCIPLINARY; Physical Sciences; Science & Technology; BUTYRYLCHOLINESTERASE; molecular docking; THERAPY; carbamate derivatives; non-covalent interactions; GENE; ALZHEIMERS-DISEASE; HYPOTHESIS; DYNAMICS; ACETYLCHOLINESTERASE INHIBITORS; TRANSITION-STATES; butyrylcholinesterase inhibitors
• ISSN: 0103-5053; 1678-4790; 1678-4790
• DOI: 10.5935/0103-5053.20160041

The present study describes the synthesis, assessment of the anticholinesterase activity and the inhibition type of novel cis- and trans-3-arylaminocyclohexyl N,N-dimethylcarbamates. In vitro inhibition assay by Ellman's method with human blood samples showed that carbamates were selective for butyrylcholinesterase (BuChE) with compound concentration that inhibits 50% of enzyme activity (IC50) between 0.11 and 0.18 mmol L-1. cis- and trans-3-(4-Methoxyphenylamino) cyclohexyl N,N-dimethylcarbamate hydrochloride were the most active for BuChE, showing that the presence of methoxyl group enhanced the anticholinesterase activity. The enzyme kinetics studies indicate a noncompetitive inhibition against acetylcholinesterase (AChE) and mixed type inhibition for BuChE. Molecular modeling studies confirm the ability of carbamates to bind both the active and peripheral sites of the BuChE.