The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides
A computational docking approach, in combination with the Hammett relationship, has been employed to evaluate the electronic influence of substituents on ligand binding and the active site-directed inhibitory potency on acetylcholinesterase using nine N-aryl-substituted succinimides. Our results indicate that electron-withdrawing groups attached to benzene moiety of the compounds favor the inhibitory potency while electron-donating groups do not. This fact was confirmed by performing kinetic experiments on acetylcholinesterase from Electrophorus electricus; the experiments showed that para-substituted-NO2 compound inhibits better than para-substituted-OMe and -H derivatives. This approach may be useful for the rationalization of drugs design, as well as the mechanism of the active site.
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Sociedad Química de México A.C.
2007
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oai:scielo:S1870-249X20070004000102016-03-03The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted SuccinimidesGuevara-Salazar,J. AlbertoEspinoza-Fonseca,MichelBeltrán,Hiram I.Correa-Basurto,JoséQuintana Zavala,DeliaTrujillo-Ferrara,José G. Acetylcholinesterase Hammett Relationship Docking N-aryl-substituted-succinimides A computational docking approach, in combination with the Hammett relationship, has been employed to evaluate the electronic influence of substituents on ligand binding and the active site-directed inhibitory potency on acetylcholinesterase using nine N-aryl-substituted succinimides. Our results indicate that electron-withdrawing groups attached to benzene moiety of the compounds favor the inhibitory potency while electron-donating groups do not. This fact was confirmed by performing kinetic experiments on acetylcholinesterase from Electrophorus electricus; the experiments showed that para-substituted-NO2 compound inhibits better than para-substituted-OMe and -H derivatives. This approach may be useful for the rationalization of drugs design, as well as the mechanism of the active site.info:eu-repo/semantics/openAccessSociedad Química de México A.C.Journal of the Mexican Chemical Society v.51 n.4 20072007-12-01info:eu-repo/semantics/articletext/htmlhttp://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1870-249X2007000400010en |
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Guevara-Salazar,J. Alberto Espinoza-Fonseca,Michel Beltrán,Hiram I. Correa-Basurto,José Quintana Zavala,Delia Trujillo-Ferrara,José G. |
| spellingShingle |
Guevara-Salazar,J. Alberto Espinoza-Fonseca,Michel Beltrán,Hiram I. Correa-Basurto,José Quintana Zavala,Delia Trujillo-Ferrara,José G. The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| author_facet |
Guevara-Salazar,J. Alberto Espinoza-Fonseca,Michel Beltrán,Hiram I. Correa-Basurto,José Quintana Zavala,Delia Trujillo-Ferrara,José G. |
| author_sort |
Guevara-Salazar,J. Alberto |
| title |
The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| title_short |
The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| title_full |
The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| title_fullStr |
The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| title_full_unstemmed |
The Electronic Influence on the Active Site-Directed Inhibition of Acetylcholinesterase by N-aryl-Substituted Succinimides |
| title_sort |
electronic influence on the active site-directed inhibition of acetylcholinesterase by n-aryl-substituted succinimides |
| description |
A computational docking approach, in combination with the Hammett relationship, has been employed to evaluate the electronic influence of substituents on ligand binding and the active site-directed inhibitory potency on acetylcholinesterase using nine N-aryl-substituted succinimides. Our results indicate that electron-withdrawing groups attached to benzene moiety of the compounds favor the inhibitory potency while electron-donating groups do not. This fact was confirmed by performing kinetic experiments on acetylcholinesterase from Electrophorus electricus; the experiments showed that para-substituted-NO2 compound inhibits better than para-substituted-OMe and -H derivatives. This approach may be useful for the rationalization of drugs design, as well as the mechanism of the active site. |
| publisher |
Sociedad Química de México A.C. |
| publishDate |
2007 |
| url |
http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S1870-249X2007000400010 |
| work_keys_str_mv |
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