Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis

Autores
Garro Martínez, Juan C,; Vega Hissi, Esteban Gabriel; Andrada, Matias Fernando; Duchowicz, Pablo Román; Torrens, Francisco; Estrada, Mario R.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.
Fil: Garro Martínez, Juan C,. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis; Argentina
Fil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
Fil: Andrada, Matias Fernando. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Torrens, Francisco. Universidad de Valencia; España
Fil: Estrada, Mario R.. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
Materia
Lacosamide
Qsar
Anticonvulsant
Docking
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:11336/7485
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7485
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR AnalysisGarro Martínez, Juan C,Vega Hissi, Esteban GabrielAndrada, Matias FernandoDuchowicz, Pablo RománTorrens, FranciscoEstrada, Mario R.LacosamideQsarAnticonvulsantDockinghttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.Fil: Garro Martínez, Juan C,. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis; ArgentinaFil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; ArgentinaFil: Andrada, Matias Fernando. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; ArgentinaFil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Torrens, Francisco. Universidad de Valencia; EspañaFil: Estrada, Mario R.. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; ArgentinaBentham Science Publishers2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/zipapplication/pdfapplication/ziphttp://hdl.handle.net/11336/7485Garro Martínez, Juan C,; Vega Hissi, Esteban Gabriel; Andrada, Matias Fernando; Duchowicz, Pablo Román; Torrens, Francisco; et al.; Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis; Bentham Science Publishers; Current Computer-aided Drug Design; 10; 2; 4-2014; 160-1671573-4099enginfo:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/121515/articleinfo:eu-repo/semantics/altIdentifier/doi/10.2174/1573409910666140410123706info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-29T11:46:02Zoai:ri.conicet.gov.ar:11336/7485instacron: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:34982025-10-29 11:46:02.909CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
title Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
spellingShingle Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
Garro Martínez, Juan C,
Lacosamide
Qsar
Anticonvulsant
Docking
title_short Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
title_full Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
title_fullStr Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
title_full_unstemmed Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
title_sort Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis
dc.creator.none.fl_str_mv Garro Martínez, Juan C,
Vega Hissi, Esteban Gabriel
Andrada, Matias Fernando
Duchowicz, Pablo Román
Torrens, Francisco
Estrada, Mario R.
author Garro Martínez, Juan C,
author_facet Garro Martínez, Juan C,
Vega Hissi, Esteban Gabriel
Andrada, Matias Fernando
Duchowicz, Pablo Román
Torrens, Francisco
Estrada, Mario R.
author_role author
author2 Vega Hissi, Esteban Gabriel
Andrada, Matias Fernando
Duchowicz, Pablo Román
Torrens, Francisco
Estrada, Mario R.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Lacosamide
Qsar
Anticonvulsant
Docking
topic Lacosamide
Qsar
Anticonvulsant
Docking
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.
Fil: Garro Martínez, Juan C,. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis; Argentina
Fil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
Fil: Andrada, Matias Fernando. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Torrens, Francisco. Universidad de Valencia; España
Fil: Estrada, Mario R.. Universidad Nacional de San Luis. Facultad de Quimica, Bioquimica y Farmacia. Departamento de Quimica. Area de Quimica Fisica; Argentina
description Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
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/11336/7485
Garro Martínez, Juan C,; Vega Hissi, Esteban Gabriel; Andrada, Matias Fernando; Duchowicz, Pablo Román; Torrens, Francisco; et al.; Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis; Bentham Science Publishers; Current Computer-aided Drug Design; 10; 2; 4-2014; 160-167
1573-4099
url http://hdl.handle.net/11336/7485
identifier_str_mv Garro Martínez, Juan C,; Vega Hissi, Esteban Gabriel; Andrada, Matias Fernando; Duchowicz, Pablo Román; Torrens, Francisco; et al.; Lacosamide Derivatives with Anticonvulsant Activity as Carbonic Anhydrase Inhibitors. Molecular Modeling, Docking and QSAR Analysis; Bentham Science Publishers; Current Computer-aided Drug Design; 10; 2; 4-2014; 160-167
1573-4099
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.eurekaselect.com/121515/article
info:eu-repo/semantics/altIdentifier/doi/10.2174/1573409910666140410123706
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/zip
application/pdf
application/zip
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
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
_version_ 1847426439944601600
score 13.10058

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