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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/136379
Ver los metadatos del registro completo
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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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1844613026862333952 |
score |
13.070432 |