Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical st...

Autores
Mastrantonio Garrido, Guido Enrique; Mack, Hans-Georg; Della Védova, Carlos Omar
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Organophosphorus pesticides are the most common classes involved in poisonings related to pesticides. We used inhibitory ability on enzymatic activity of acetylcholinesterase activity and molecular mechanics or ab initio methods of molecular modelling to perform a theoretical approach of the enzyme interaction mechanism of these compounds. Kinetic values for strong and weak inhibitors were measured in a high amplitude range for affinity (Kₐ) and phosphorylation constants (Kₚ). To quantitatively describe the conformational behaviour of these molecules, conformational descriptors of free molecules were developed. Quantitative structure activity relationships (QSARs) were constructed with inhibition kinetic values and their molecular descriptors. The conformational descriptors show a high degree of correlation with the kinetic behaviour of these molecules. A positive correlation between the conformational freedom of the studied molecules with Kₐ is observed. This study allows us to reinterpret the organophosphorus cholinesterase inhibition mechanism and consequently the ‘thiono’ and ‘thiolo effect’ based on a global ‘chalcogen effect’.
Facultad de Ciencias Exactas
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
Centro de Química Inorgánica
Materia
Química
Acetylcholinesterase
Conformational behaviour
Organophosphorus compounds
Structure activity relationship
Toxicity mechanism
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/133545
Acceder
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oai_identifier_str oai:sedici.unlp.edu.ar:10915/133545
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical studyMastrantonio Garrido, Guido EnriqueMack, Hans-GeorgDella Védova, Carlos OmarQuímicaAcetylcholinesteraseConformational behaviourOrganophosphorus compoundsStructure activity relationshipToxicity mechanismOrganophosphorus pesticides are the most common classes involved in poisonings related to pesticides. We used inhibitory ability on enzymatic activity of acetylcholinesterase activity and molecular mechanics or <i>ab initio</i> methods of molecular modelling to perform a theoretical approach of the enzyme interaction mechanism of these compounds. Kinetic values for strong and weak inhibitors were measured in a high amplitude range for affinity (Kₐ) and phosphorylation constants (Kₚ). To quantitatively describe the conformational behaviour of these molecules, conformational descriptors of free molecules were developed. Quantitative structure activity relationships (QSARs) were constructed with inhibition kinetic values and their molecular descriptors. The conformational descriptors show a high degree of correlation with the kinetic behaviour of these molecules. A positive correlation between the conformational freedom of the studied molecules with Kₐ is observed. This study allows us to reinterpret the organophosphorus cholinesterase inhibition mechanism and consequently the ‘thiono’ and ‘thiolo effect’ based on a global ‘chalcogen effect’.Facultad de Ciencias ExactasPlanta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema CientíficoCentro de Química Inorgánica2008-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf813-821http://sedici.unlp.edu.ar/handle/10915/133545enginfo:eu-repo/semantics/altIdentifier/issn/0948-5023info:eu-repo/semantics/altIdentifier/issn/1610-2940info:eu-repo/semantics/altIdentifier/doi/10.1007/s00894-008-0321-0info:eu-repo/semantics/altIdentifier/pmid/18581151info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-11-12T10:56:09Zoai:sedici.unlp.edu.ar:10915/133545Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-11-12 10:56:09.959SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
title Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
spellingShingle Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
Mastrantonio Garrido, Guido Enrique
Química
Acetylcholinesterase
Conformational behaviour
Organophosphorus compounds
Structure activity relationship
Toxicity mechanism
title_short Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
title_full Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
title_fullStr Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
title_full_unstemmed Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
title_sort Interpretation of the mechanism of acetylcholinesterase inhibition ability by organophosphorus compounds through a new conformational descriptor. an experimental and theoretical study
dc.creator.none.fl_str_mv Mastrantonio Garrido, Guido Enrique
Mack, Hans-Georg
Della Védova, Carlos Omar
author Mastrantonio Garrido, Guido Enrique
author_facet Mastrantonio Garrido, Guido Enrique
Mack, Hans-Georg
Della Védova, Carlos Omar
author_role author
author2 Mack, Hans-Georg
Della Védova, Carlos Omar
author2_role author
author
dc.subject.none.fl_str_mv Química
Acetylcholinesterase
Conformational behaviour
Organophosphorus compounds
Structure activity relationship
Toxicity mechanism
topic Química
Acetylcholinesterase
Conformational behaviour
Organophosphorus compounds
Structure activity relationship
Toxicity mechanism
dc.description.none.fl_txt_mv Organophosphorus pesticides are the most common classes involved in poisonings related to pesticides. We used inhibitory ability on enzymatic activity of acetylcholinesterase activity and molecular mechanics or <i>ab initio</i> methods of molecular modelling to perform a theoretical approach of the enzyme interaction mechanism of these compounds. Kinetic values for strong and weak inhibitors were measured in a high amplitude range for affinity (Kₐ) and phosphorylation constants (Kₚ). To quantitatively describe the conformational behaviour of these molecules, conformational descriptors of free molecules were developed. Quantitative structure activity relationships (QSARs) were constructed with inhibition kinetic values and their molecular descriptors. The conformational descriptors show a high degree of correlation with the kinetic behaviour of these molecules. A positive correlation between the conformational freedom of the studied molecules with Kₐ is observed. This study allows us to reinterpret the organophosphorus cholinesterase inhibition mechanism and consequently the ‘thiono’ and ‘thiolo effect’ based on a global ‘chalcogen effect’.
Facultad de Ciencias Exactas
Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico
Centro de Química Inorgánica
description Organophosphorus pesticides are the most common classes involved in poisonings related to pesticides. We used inhibitory ability on enzymatic activity of acetylcholinesterase activity and molecular mechanics or <i>ab initio</i> methods of molecular modelling to perform a theoretical approach of the enzyme interaction mechanism of these compounds. Kinetic values for strong and weak inhibitors were measured in a high amplitude range for affinity (Kₐ) and phosphorylation constants (Kₚ). To quantitatively describe the conformational behaviour of these molecules, conformational descriptors of free molecules were developed. Quantitative structure activity relationships (QSARs) were constructed with inhibition kinetic values and their molecular descriptors. The conformational descriptors show a high degree of correlation with the kinetic behaviour of these molecules. A positive correlation between the conformational freedom of the studied molecules with Kₐ is observed. This study allows us to reinterpret the organophosphorus cholinesterase inhibition mechanism and consequently the ‘thiono’ and ‘thiolo effect’ based on a global ‘chalcogen effect’.
publishDate 2008
dc.date.none.fl_str_mv 2008-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/133545
url http://sedici.unlp.edu.ar/handle/10915/133545
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0948-5023
info:eu-repo/semantics/altIdentifier/issn/1610-2940
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00894-008-0321-0
info:eu-repo/semantics/altIdentifier/pmid/18581151
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
813-821
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.223955

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