Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study

Autores
Campos, Ludmila Estefanía; Garibotto, Francisco Matías; Vettorazzi, Marcela Cristina; Angelina, Emilio Luis; Alvarez, Sergio Eduardo; Enriz, Ricardo Daniel
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Recently we reported two new structural scaffolds as potential inhibitors of BRAF; both series of compounds were studied in greater depth in the present work. Our results indicate that the new substituted piperazinylpropandiols derivatives evaluated here do not show significantly better activities to that previously reported for the structure chosen as starting structure. In contrast the results obtained for the other series were more positive. We report now new hydroxynaphthalenecarboxamides with significant inhibitory activity on BRAF. In order to better understand these experimental results, wecarried out a molecular modeling study using different combined techniques. While the simulations using simple techniques such as docking and DM simulations allowed us to explain which the best structural scaffold, these results is do not allow to explain why compounds with substituents in different spatial positions have similar inhibitory effects. In this sense, the use of MD/QTAIM combined calculations allow to explain in detail the molecular interactions that stabilize the different molecular complexes reported here. Another interesting contribution of this study is that the different molecular interactions that stabilize the complexes have been analyzed in depth. The QTAIM results indicatethat the different spatial dispositions of the substituents (ortho, meta and para) allow to establish alternative interactions with Asp594 or with Lis483 depending on their spatial arrangement. This result is in agreement to those observed for vemurafenib and dabrafenib. This structural information is important for the design of new inhibitors with this type of structural scaffold.
Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Angelina, Emilio Luis. 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. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica
San Luis
Argentina
Sociedad Argentina de Biofísica
Universidad Nacional de San Luis
Materia
Cancer Melanoma
Vemurafenib
Molecular Modelling
MD/QTAIM
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:11336/181340
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental studyCampos, Ludmila EstefaníaGaribotto, Francisco MatíasVettorazzi, Marcela CristinaAngelina, Emilio LuisAlvarez, Sergio EduardoEnriz, Ricardo DanielCancer MelanomaVemurafenibMolecular ModellingMD/QTAIMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Recently we reported two new structural scaffolds as potential inhibitors of BRAF; both series of compounds were studied in greater depth in the present work. Our results indicate that the new substituted piperazinylpropandiols derivatives evaluated here do not show significantly better activities to that previously reported for the structure chosen as starting structure. In contrast the results obtained for the other series were more positive. We report now new hydroxynaphthalenecarboxamides with significant inhibitory activity on BRAF. In order to better understand these experimental results, wecarried out a molecular modeling study using different combined techniques. While the simulations using simple techniques such as docking and DM simulations allowed us to explain which the best structural scaffold, these results is do not allow to explain why compounds with substituents in different spatial positions have similar inhibitory effects. In this sense, the use of MD/QTAIM combined calculations allow to explain in detail the molecular interactions that stabilize the different molecular complexes reported here. Another interesting contribution of this study is that the different molecular interactions that stabilize the complexes have been analyzed in depth. The QTAIM results indicatethat the different spatial dispositions of the substituents (ortho, meta and para) allow to establish alternative interactions with Asp594 or with Lis483 depending on their spatial arrangement. This result is in agreement to those observed for vemurafenib and dabrafenib. This structural information is important for the design of new inhibitors with this type of structural scaffold.Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Angelina, Emilio Luis. 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. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaXLVIII Reunión Anual de la Sociedad Argentina de BiofísicaSan LuisArgentinaSociedad Argentina de BiofísicaUniversidad Nacional de San LuisSociedad Argentina de Biofísica2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/181340Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 162-162978-987-27591-7-9CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:20Zoai:ri.conicet.gov.ar:11336/181340instacron: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 10:01:20.484CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
title Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
spellingShingle Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
Campos, Ludmila Estefanía
Cancer Melanoma
Vemurafenib
Molecular Modelling
MD/QTAIM
title_short Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
title_full Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
title_fullStr Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
title_full_unstemmed Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
title_sort Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study
dc.creator.none.fl_str_mv Campos, Ludmila Estefanía
Garibotto, Francisco Matías
Vettorazzi, Marcela Cristina
Angelina, Emilio Luis
Alvarez, Sergio Eduardo
Enriz, Ricardo Daniel
author Campos, Ludmila Estefanía
author_facet Campos, Ludmila Estefanía
Garibotto, Francisco Matías
Vettorazzi, Marcela Cristina
Angelina, Emilio Luis
Alvarez, Sergio Eduardo
Enriz, Ricardo Daniel
author_role author
author2 Garibotto, Francisco Matías
Vettorazzi, Marcela Cristina
Angelina, Emilio Luis
Alvarez, Sergio Eduardo
Enriz, Ricardo Daniel
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cancer Melanoma
Vemurafenib
Molecular Modelling
MD/QTAIM
topic Cancer Melanoma
Vemurafenib
Molecular Modelling
MD/QTAIM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Recently we reported two new structural scaffolds as potential inhibitors of BRAF; both series of compounds were studied in greater depth in the present work. Our results indicate that the new substituted piperazinylpropandiols derivatives evaluated here do not show significantly better activities to that previously reported for the structure chosen as starting structure. In contrast the results obtained for the other series were more positive. We report now new hydroxynaphthalenecarboxamides with significant inhibitory activity on BRAF. In order to better understand these experimental results, wecarried out a molecular modeling study using different combined techniques. While the simulations using simple techniques such as docking and DM simulations allowed us to explain which the best structural scaffold, these results is do not allow to explain why compounds with substituents in different spatial positions have similar inhibitory effects. In this sense, the use of MD/QTAIM combined calculations allow to explain in detail the molecular interactions that stabilize the different molecular complexes reported here. Another interesting contribution of this study is that the different molecular interactions that stabilize the complexes have been analyzed in depth. The QTAIM results indicatethat the different spatial dispositions of the substituents (ortho, meta and para) allow to establish alternative interactions with Asp594 or with Lis483 depending on their spatial arrangement. This result is in agreement to those observed for vemurafenib and dabrafenib. This structural information is important for the design of new inhibitors with this type of structural scaffold.
Fil: Campos, Ludmila Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Garibotto, Francisco Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Vettorazzi, Marcela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Angelina, Emilio Luis. 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. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; Argentina
Fil: Alvarez, Sergio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
XLVIII Reunión Anual de la Sociedad Argentina de Biofísica
San Luis
Argentina
Sociedad Argentina de Biofísica
Universidad Nacional de San Luis
description Recently we reported two new structural scaffolds as potential inhibitors of BRAF; both series of compounds were studied in greater depth in the present work. Our results indicate that the new substituted piperazinylpropandiols derivatives evaluated here do not show significantly better activities to that previously reported for the structure chosen as starting structure. In contrast the results obtained for the other series were more positive. We report now new hydroxynaphthalenecarboxamides with significant inhibitory activity on BRAF. In order to better understand these experimental results, wecarried out a molecular modeling study using different combined techniques. While the simulations using simple techniques such as docking and DM simulations allowed us to explain which the best structural scaffold, these results is do not allow to explain why compounds with substituents in different spatial positions have similar inhibitory effects. In this sense, the use of MD/QTAIM combined calculations allow to explain in detail the molecular interactions that stabilize the different molecular complexes reported here. Another interesting contribution of this study is that the different molecular interactions that stabilize the complexes have been analyzed in depth. The QTAIM results indicatethat the different spatial dispositions of the substituents (ortho, meta and para) allow to establish alternative interactions with Asp594 or with Lis483 depending on their spatial arrangement. This result is in agreement to those observed for vemurafenib and dabrafenib. This structural information is important for the design of new inhibitors with this type of structural scaffold.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
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status_str publishedVersion
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dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/181340
Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 162-162
978-987-27591-7-9
CONICET Digital
CONICET
url http://hdl.handle.net/11336/181340
identifier_str_mv Hidroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of braf inhibitors. A theoretical and experimental study; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; San Luis; Argentina; 2019; 162-162
978-987-27591-7-9
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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