Structural and electronic properties of tyrosine kinases inhibitors

Autores
Santillán, Marta B.; Tomas Vert, Francisco; Aulló, Josep M.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Protein tyrosine kinases (TKs) regulate cell proliferation, cell differentiation, and play a fundamental role in signal transduction pathway. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases was related to diseases such as cancer, atherosclerosis and psoriasis. For the present study, we selected a number of structurally related ATP-binding site inhibitors of EGF-receptors of diverse classes. Molecular properties of competitive inhibitors are key features for the action mechanism of these compounds. We performed a theoretical study at the RHF/6-311G* level of theory, in order to correlate the molecular parameters with the biological inhibitory activities. Species stability as evaluated by ionization potentials as well as the E(HOMO)-E(LUMO) energy gap, is in very good correlation with higher inhibitory potency (IP). The most active species, 1, 5, 6,10,11 and 12 exhibited strongly negative charged atoms over the C6 and C7 positions, the higher IP, higher mu and higher energy gap. In summary, a good correlation was observed between the molecular parameters, such as ionization potential, dipolar moment and E(HOMO)-E(LUMO) energy gap and inhibitory potency, suggesting that these properties play an important role for the interaction at the ATP-binding site of EGF-receptors.
Fil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Tomas Vert, Francisco. Universidad de Valencia; España
Fil: Aulló, Josep M.. Universidad de Valencia; España
Fil: Jauregui, Esteban Adrian. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Ciuffo, Gladys Maria. 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. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Materia
EGF receptors
Tyrosine kinase activity
Selective inhibitors
Molecular properties
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:11336/136437
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/136437
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Structural and electronic properties of tyrosine kinases inhibitorsSantillán, Marta B.Tomas Vert, FranciscoAulló, Josep M.Jauregui, Esteban AdrianCiuffo, Gladys MariaEGF receptorsTyrosine kinase activitySelective inhibitorsMolecular propertieshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Protein tyrosine kinases (TKs) regulate cell proliferation, cell differentiation, and play a fundamental role in signal transduction pathway. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases was related to diseases such as cancer, atherosclerosis and psoriasis. For the present study, we selected a number of structurally related ATP-binding site inhibitors of EGF-receptors of diverse classes. Molecular properties of competitive inhibitors are key features for the action mechanism of these compounds. We performed a theoretical study at the RHF/6-311G* level of theory, in order to correlate the molecular parameters with the biological inhibitory activities. Species stability as evaluated by ionization potentials as well as the E(HOMO)-E(LUMO) energy gap, is in very good correlation with higher inhibitory potency (IP). The most active species, 1, 5, 6,10,11 and 12 exhibited strongly negative charged atoms over the C6 and C7 positions, the higher IP, higher mu and higher energy gap. In summary, a good correlation was observed between the molecular parameters, such as ionization potential, dipolar moment and E(HOMO)-E(LUMO) energy gap and inhibitory potency, suggesting that these properties play an important role for the interaction at the ATP-binding site of EGF-receptors.Fil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Tomas Vert, Francisco. Universidad de Valencia; EspañaFil: Aulló, Josep M.. Universidad de Valencia; EspañaFil: Jauregui, Esteban Adrian. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Ciuffo, Gladys Maria. 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. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaC M B Association2003-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/136437Santillán, Marta B.; Tomas Vert, Francisco; Aulló, Josep M.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structural and electronic properties of tyrosine kinases inhibitors; C M B Association; Cellular and Molecular Biology; 49; 6; 9-2003; 929-9370145-5680CONICET DigitalCONICETenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:41Zoai:ri.conicet.gov.ar:11336/136437instacron: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:34982025-09-29 09:46:42.21CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structural and electronic properties of tyrosine kinases inhibitors
title Structural and electronic properties of tyrosine kinases inhibitors
spellingShingle Structural and electronic properties of tyrosine kinases inhibitors
Santillán, Marta B.
EGF receptors
Tyrosine kinase activity
Selective inhibitors
Molecular properties
title_short Structural and electronic properties of tyrosine kinases inhibitors
title_full Structural and electronic properties of tyrosine kinases inhibitors
title_fullStr Structural and electronic properties of tyrosine kinases inhibitors
title_full_unstemmed Structural and electronic properties of tyrosine kinases inhibitors
title_sort Structural and electronic properties of tyrosine kinases inhibitors
dc.creator.none.fl_str_mv Santillán, Marta B.
Tomas Vert, Francisco
Aulló, Josep M.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author Santillán, Marta B.
author_facet Santillán, Marta B.
Tomas Vert, Francisco
Aulló, Josep M.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author_role author
author2 Tomas Vert, Francisco
Aulló, Josep M.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author2_role author
author
author
author
dc.subject.none.fl_str_mv EGF receptors
Tyrosine kinase activity
Selective inhibitors
Molecular properties
topic EGF receptors
Tyrosine kinase activity
Selective inhibitors
Molecular properties
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Protein tyrosine kinases (TKs) regulate cell proliferation, cell differentiation, and play a fundamental role in signal transduction pathway. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases was related to diseases such as cancer, atherosclerosis and psoriasis. For the present study, we selected a number of structurally related ATP-binding site inhibitors of EGF-receptors of diverse classes. Molecular properties of competitive inhibitors are key features for the action mechanism of these compounds. We performed a theoretical study at the RHF/6-311G* level of theory, in order to correlate the molecular parameters with the biological inhibitory activities. Species stability as evaluated by ionization potentials as well as the E(HOMO)-E(LUMO) energy gap, is in very good correlation with higher inhibitory potency (IP). The most active species, 1, 5, 6,10,11 and 12 exhibited strongly negative charged atoms over the C6 and C7 positions, the higher IP, higher mu and higher energy gap. In summary, a good correlation was observed between the molecular parameters, such as ionization potential, dipolar moment and E(HOMO)-E(LUMO) energy gap and inhibitory potency, suggesting that these properties play an important role for the interaction at the ATP-binding site of EGF-receptors.
Fil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Tomas Vert, Francisco. Universidad de Valencia; España
Fil: Aulló, Josep M.. Universidad de Valencia; España
Fil: Jauregui, Esteban Adrian. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Ciuffo, Gladys Maria. 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. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
description Protein tyrosine kinases (TKs) regulate cell proliferation, cell differentiation, and play a fundamental role in signal transduction pathway. Uncontrolled signaling from receptor tyrosine kinases and intracellular tyrosine kinases was related to diseases such as cancer, atherosclerosis and psoriasis. For the present study, we selected a number of structurally related ATP-binding site inhibitors of EGF-receptors of diverse classes. Molecular properties of competitive inhibitors are key features for the action mechanism of these compounds. We performed a theoretical study at the RHF/6-311G* level of theory, in order to correlate the molecular parameters with the biological inhibitory activities. Species stability as evaluated by ionization potentials as well as the E(HOMO)-E(LUMO) energy gap, is in very good correlation with higher inhibitory potency (IP). The most active species, 1, 5, 6,10,11 and 12 exhibited strongly negative charged atoms over the C6 and C7 positions, the higher IP, higher mu and higher energy gap. In summary, a good correlation was observed between the molecular parameters, such as ionization potential, dipolar moment and E(HOMO)-E(LUMO) energy gap and inhibitory potency, suggesting that these properties play an important role for the interaction at the ATP-binding site of EGF-receptors.
publishDate 2003
dc.date.none.fl_str_mv 2003-09
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/11336/136437
Santillán, Marta B.; Tomas Vert, Francisco; Aulló, Josep M.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structural and electronic properties of tyrosine kinases inhibitors; C M B Association; Cellular and Molecular Biology; 49; 6; 9-2003; 929-937
0145-5680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/136437
identifier_str_mv Santillán, Marta B.; Tomas Vert, Francisco; Aulló, Josep M.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structural and electronic properties of tyrosine kinases inhibitors; C M B Association; Cellular and Molecular Biology; 49; 6; 9-2003; 929-937
0145-5680
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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
dc.publisher.none.fl_str_mv C M B Association
publisher.none.fl_str_mv C M B Association
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 13.070432

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