3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity

Autores
Angelina, Emilio Luis; Andujar, Sebastian Antonio; Moreno, Laura; Garibotto, Francisco Matías; Párraga, Javier; Peruchena, Nelida Maria; Cabedo, Nuria; Villeco, Margarita; Cortes, Diego; Enriz, Ricardo Daniel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA.
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Andujar, Sebastian Antonio. Universidad Nacional del Nordeste. Facultad de Cs.exactas Naturales y Agrimensura. Departamento de Quimica. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Moreno, Laura. Universidad de Valencia; España
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Párraga, Javier. Universidad de Valencia; España
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabedo, Nuria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Villeco, Margarita. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; Argentina
Fil: Cortes, Diego. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Materia
3-Chlorotyramine
Md Simulations
Qtaim Analysis
D2 Dopamine Receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14649
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14649
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinityAngelina, Emilio LuisAndujar, Sebastian AntonioMoreno, LauraGaribotto, Francisco MatíasPárraga, JavierPeruchena, Nelida MariaCabedo, NuriaVilleco, MargaritaCortes, DiegoEnriz, Ricardo Daniel3-ChlorotyramineMd SimulationsQtaim AnalysisD2 Dopamine Receptorhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA.Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; ArgentinaFil: Andujar, Sebastian Antonio. Universidad Nacional del Nordeste. Facultad de Cs.exactas Naturales y Agrimensura. Departamento de Quimica. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Moreno, Laura. Universidad de Valencia; EspañaFil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Párraga, Javier. Universidad de Valencia; EspañaFil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabedo, Nuria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; ArgentinaFil: Villeco, Margarita. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; ArgentinaFil: Cortes, Diego. Universidad de Valencia; EspañaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaWiley VCH Verlag2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14649Angelina, Emilio Luis; Andujar, Sebastian Antonio; Moreno, Laura; Garibotto, Francisco Matías; Párraga, Javier; et al.; 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity; Wiley VCH Verlag; Molecular Informatics; 34; 1; 2-2015; 28-431868-17431868-1751enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/minf.201400093/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1002/minf.201400093info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:16Zoai:ri.conicet.gov.ar:11336/14649instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:16.789CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
title 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
spellingShingle 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
Angelina, Emilio Luis
3-Chlorotyramine
Md Simulations
Qtaim Analysis
D2 Dopamine Receptor
title_short 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
title_full 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
title_fullStr 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
title_full_unstemmed 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
title_sort 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity
dc.creator.none.fl_str_mv Angelina, Emilio Luis
Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco Matías
Párraga, Javier
Peruchena, Nelida Maria
Cabedo, Nuria
Villeco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
author Angelina, Emilio Luis
author_facet Angelina, Emilio Luis
Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco Matías
Párraga, Javier
Peruchena, Nelida Maria
Cabedo, Nuria
Villeco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
author_role author
author2 Andujar, Sebastian Antonio
Moreno, Laura
Garibotto, Francisco Matías
Párraga, Javier
Peruchena, Nelida Maria
Cabedo, Nuria
Villeco, Margarita
Cortes, Diego
Enriz, Ricardo Daniel
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 3-Chlorotyramine
Md Simulations
Qtaim Analysis
D2 Dopamine Receptor
topic 3-Chlorotyramine
Md Simulations
Qtaim Analysis
D2 Dopamine Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA.
Fil: Angelina, Emilio Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Andujar, Sebastian Antonio. Universidad Nacional del Nordeste. Facultad de Cs.exactas Naturales y Agrimensura. Departamento de Quimica. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Moreno, Laura. Universidad de Valencia; España
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Párraga, Javier. Universidad de Valencia; España
Fil: Peruchena, Nelida Maria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cabedo, Nuria. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas y Naturales y Agrimensura. Departamento de Química. Laboratorio de Estructura Molecular y Propiedades; Argentina
Fil: Villeco, Margarita. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Orgánica; Argentina
Fil: Cortes, Diego. Universidad de Valencia; España
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
description We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2-DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2-DR to that reported for DA.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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://hdl.handle.net/11336/14649
Angelina, Emilio Luis; Andujar, Sebastian Antonio; Moreno, Laura; Garibotto, Francisco Matías; Párraga, Javier; et al.; 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity; Wiley VCH Verlag; Molecular Informatics; 34; 1; 2-2015; 28-43
1868-1743
1868-1751
url http://hdl.handle.net/11336/14649
identifier_str_mv Angelina, Emilio Luis; Andujar, Sebastian Antonio; Moreno, Laura; Garibotto, Francisco Matías; Párraga, Javier; et al.; 3-Chlorotyramine acting as ligand of the d2 dopamine receptor: molecular modeling, synthesis and d2 receptor affinity; Wiley VCH Verlag; Molecular Informatics; 34; 1; 2-2015; 28-43
1868-1743
1868-1751
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/minf.201400093/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1002/minf.201400093
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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