Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling
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.
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Sociedade Brasileira de Química
2016
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oai:scielo:S0103-505320160009016162016-09-14Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular ModelingYamazaki,Diego A. S.Cândido,Augusto A.Bagatin,Mariane C.Machinski Jr.,MiguelMossini,,Simone A. G.Pontes,Rodrigo M.Rosa,Fernanda A.Basso,Ernani A.Gauze,Gisele F. carbamate derivatives butyrylcholinesterase inhibitors molecular docking non-covalent interactions 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.info:eu-repo/semantics/openAccessSociedade Brasileira de QuímicaJournal of the Brazilian Chemical Society v.27 n.9 20162016-09-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000901616en10.5935/0103-5053.20160041 |
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Yamazaki,Diego A. S. Cândido,Augusto A. Bagatin,Mariane C. Machinski Jr.,Miguel Mossini,,Simone A. G. Pontes,Rodrigo M. Rosa,Fernanda A. Basso,Ernani A. Gauze,Gisele F. |
spellingShingle |
Yamazaki,Diego A. S. Cândido,Augusto A. Bagatin,Mariane C. Machinski Jr.,Miguel Mossini,,Simone A. G. Pontes,Rodrigo M. Rosa,Fernanda A. Basso,Ernani A. Gauze,Gisele F. Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
author_facet |
Yamazaki,Diego A. S. Cândido,Augusto A. Bagatin,Mariane C. Machinski Jr.,Miguel Mossini,,Simone A. G. Pontes,Rodrigo M. Rosa,Fernanda A. Basso,Ernani A. Gauze,Gisele F. |
author_sort |
Yamazaki,Diego A. S. |
title |
Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
title_short |
Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
title_full |
Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
title_fullStr |
Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
title_full_unstemmed |
Cholinesterases Inhibition by Novel cis- and trans-3-Arylaminocyclohexyl N,N-Dimethylcarbamates: Biological Evaluation and Molecular Modeling |
title_sort |
cholinesterases inhibition by novel cis- and trans-3-arylaminocyclohexyl n,n-dimethylcarbamates: biological evaluation and molecular modeling |
description |
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. |
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Sociedade Brasileira de Química |
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2016 |
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http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000901616 |
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