Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach

Autores
Morales, Elba Mirta; Santillán, Marta B.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria
Año de publicación
2002
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Nitric oxide (NO) has become an important intracellular and intercellular signal molecule and inhibition of the enzyme which produces NO (NOS, NO synthase) become a major goal for pharmacological researchers. We performed a complete search for the lowest-energy conformations at the AM1 calculation level, for zwitter-ionic species of NOS inhibitors, analogs to L-Arg. The lowest- energy conformations obtained were fully optimized at the ab initio theory levels: HF/3-21G and HF/6-31G*. L-NNA, L-NMA and L-CPA exhibited a conformational behavior quite comparable to that of L-Arg. L-NIL, L-NIO and L-NAME achieved to completely different conformations when compared to L-Arg, L-NIL, highly selective for the inducible isoform of NOS, exhibited conformational as well as charge distribution differences compared to L-Arg. L-NAME and L-NNA are highly selective compounds for the constitutive isoforms. Both compounds share the chain lengths of L-Arg and bear a nitro-substituent over the guanidinium group, which causes changes on the net atomic charges of the N-guanidinium atoms. Moreover, differences were observed on net atomic charges and density distribution analyzed by means of molecular electrostatic potentials (MEPs). These differences might be of great importance at determining the selectivity of the different inhibitors. On the basis of the conformational and molecular properties of the different NOS inhibitors and the selectivity of the analogs studied, we propose the requirements for the different NOS isoforms.
Fil: Morales, Elba Mirta. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
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. Departamento de Bioquímica y Ciencias Biológicas; Argentina
Materia
NO synthase
Substrate analogs
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:11336/136379

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network_name_str CONICET Digital (CONICET)
spelling Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approachMorales, Elba MirtaSantillán, Marta B.Jauregui, Esteban AdrianCiuffo, Gladys MariaNO synthaseSubstrate analogsSelective inhibitorsMolecular propertieshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Nitric oxide (NO) has become an important intracellular and intercellular signal molecule and inhibition of the enzyme which produces NO (NOS, NO synthase) become a major goal for pharmacological researchers. We performed a complete search for the lowest-energy conformations at the AM1 calculation level, for zwitter-ionic species of NOS inhibitors, analogs to L-Arg. The lowest- energy conformations obtained were fully optimized at the ab initio theory levels: HF/3-21G and HF/6-31G*. L-NNA, L-NMA and L-CPA exhibited a conformational behavior quite comparable to that of L-Arg. L-NIL, L-NIO and L-NAME achieved to completely different conformations when compared to L-Arg, L-NIL, highly selective for the inducible isoform of NOS, exhibited conformational as well as charge distribution differences compared to L-Arg. L-NAME and L-NNA are highly selective compounds for the constitutive isoforms. Both compounds share the chain lengths of L-Arg and bear a nitro-substituent over the guanidinium group, which causes changes on the net atomic charges of the N-guanidinium atoms. Moreover, differences were observed on net atomic charges and density distribution analyzed by means of molecular electrostatic potentials (MEPs). These differences might be of great importance at determining the selectivity of the different inhibitors. On the basis of the conformational and molecular properties of the different NOS inhibitors and the selectivity of the analogs studied, we propose the requirements for the different NOS isoforms.Fil: Morales, Elba Mirta. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; ArgentinaFil: 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. Departamento de Bioquímica y Ciencias Biológicas; ArgentinaC M B Association2002-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/136379Morales, Elba Mirta; Santillán, Marta B.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach; C M B Association; Cellular and Molecular Biology; 48; 5; 7-2002; 547-5560145-56801165-158XCONICET 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 Técnicas2025-09-29T09:33:25Zoai:ri.conicet.gov.ar:11336/136379instacron: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 09:33:25.419CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
title Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
spellingShingle Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
Morales, Elba Mirta
NO synthase
Substrate analogs
Selective inhibitors
Molecular properties
title_short Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
title_full Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
title_fullStr Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
title_full_unstemmed Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
title_sort Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach
dc.creator.none.fl_str_mv Morales, Elba Mirta
Santillán, Marta B.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author Morales, Elba Mirta
author_facet Morales, Elba Mirta
Santillán, Marta B.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author_role author
author2 Santillán, Marta B.
Jauregui, Esteban Adrian
Ciuffo, Gladys Maria
author2_role author
author
author
dc.subject.none.fl_str_mv NO synthase
Substrate analogs
Selective inhibitors
Molecular properties
topic NO synthase
Substrate analogs
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 Nitric oxide (NO) has become an important intracellular and intercellular signal molecule and inhibition of the enzyme which produces NO (NOS, NO synthase) become a major goal for pharmacological researchers. We performed a complete search for the lowest-energy conformations at the AM1 calculation level, for zwitter-ionic species of NOS inhibitors, analogs to L-Arg. The lowest- energy conformations obtained were fully optimized at the ab initio theory levels: HF/3-21G and HF/6-31G*. L-NNA, L-NMA and L-CPA exhibited a conformational behavior quite comparable to that of L-Arg. L-NIL, L-NIO and L-NAME achieved to completely different conformations when compared to L-Arg, L-NIL, highly selective for the inducible isoform of NOS, exhibited conformational as well as charge distribution differences compared to L-Arg. L-NAME and L-NNA are highly selective compounds for the constitutive isoforms. Both compounds share the chain lengths of L-Arg and bear a nitro-substituent over the guanidinium group, which causes changes on the net atomic charges of the N-guanidinium atoms. Moreover, differences were observed on net atomic charges and density distribution analyzed by means of molecular electrostatic potentials (MEPs). These differences might be of great importance at determining the selectivity of the different inhibitors. On the basis of the conformational and molecular properties of the different NOS inhibitors and the selectivity of the analogs studied, we propose the requirements for the different NOS isoforms.
Fil: Morales, Elba Mirta. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
Fil: Santillán, Marta B.. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Departamento de Química; Argentina
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. Departamento de Bioquímica y Ciencias Biológicas; Argentina
description Nitric oxide (NO) has become an important intracellular and intercellular signal molecule and inhibition of the enzyme which produces NO (NOS, NO synthase) become a major goal for pharmacological researchers. We performed a complete search for the lowest-energy conformations at the AM1 calculation level, for zwitter-ionic species of NOS inhibitors, analogs to L-Arg. The lowest- energy conformations obtained were fully optimized at the ab initio theory levels: HF/3-21G and HF/6-31G*. L-NNA, L-NMA and L-CPA exhibited a conformational behavior quite comparable to that of L-Arg. L-NIL, L-NIO and L-NAME achieved to completely different conformations when compared to L-Arg, L-NIL, highly selective for the inducible isoform of NOS, exhibited conformational as well as charge distribution differences compared to L-Arg. L-NAME and L-NNA are highly selective compounds for the constitutive isoforms. Both compounds share the chain lengths of L-Arg and bear a nitro-substituent over the guanidinium group, which causes changes on the net atomic charges of the N-guanidinium atoms. Moreover, differences were observed on net atomic charges and density distribution analyzed by means of molecular electrostatic potentials (MEPs). These differences might be of great importance at determining the selectivity of the different inhibitors. On the basis of the conformational and molecular properties of the different NOS inhibitors and the selectivity of the analogs studied, we propose the requirements for the different NOS isoforms.
publishDate 2002
dc.date.none.fl_str_mv 2002-07
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/11336/136379
Morales, Elba Mirta; Santillán, Marta B.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach; C M B Association; Cellular and Molecular Biology; 48; 5; 7-2002; 547-556
0145-5680
1165-158X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/136379
identifier_str_mv Morales, Elba Mirta; Santillán, Marta B.; Jauregui, Esteban Adrian; Ciuffo, Gladys Maria; Structure-actvity relationship of nitric oxide synthase inhibitors: a theoretical approach; C M B Association; Cellular and Molecular Biology; 48; 5; 7-2002; 547-556
0145-5680
1165-158X
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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