Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin

A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (H, C, F and N) spec...

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Detalles Bibliográficos
Autores: Nieto, Carla I., Elguero, José, Acuña-Castroviejo, D.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/137193
Acceso en línea:http://hdl.handle.net/10261/137193
Access Level:acceso abierto
Palabra clave:NOS inhibitors
Crystallography
Curcumin
Fluorine derivatives
Multinuclear NMR
Pyrazoles
Tautomerism
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spelling Fluorination effects on NOS inhibitory activity of pyrazoles related to curcuminNieto, Carla I.Elguero, JoséAcuña-Castroviejo, D.NOS inhibitorsCrystallographyCurcuminFluorine derivativesMultinuclear NMRPyrazolesTautomerismA series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (H, C, F and N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1Hpyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.This work has been financed by Ministerio de Ciencia e Innovación (CTQ2010-16122) and Ministerio de Economía y Competitividad of Spain (CTQ2014-56833-R, RD12/0043/0005, and PI13-00981) and Comunidad Autónoma de Madrid (Project MADRISOLAR2, ref. S2009/PPQ-1533). One of us (C. I. Nieto) is indebted to UNED for a predoctoral fellowship (FPI “Grupos de Investigación” UNED). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer ReviewedMolecular Diversity Preservation InternationalMinisterio de Economía y Competitividad (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas (España)Universidad Nacional de Educación a Distancia (España)Ministerio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2016201620152016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/137193reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2014-56833-RS2009/PPQ-1533/MADRISOLAR2Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1371932026-05-22T06:33:51Z
dc.title.none.fl_str_mv Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
title Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
spellingShingle Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
Nieto, Carla I.
NOS inhibitors
Crystallography
Curcumin
Fluorine derivatives
Multinuclear NMR
Pyrazoles
Tautomerism
title_short Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
title_full Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
title_fullStr Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
title_full_unstemmed Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
title_sort Fluorination effects on NOS inhibitory activity of pyrazoles related to curcumin
dc.creator.none.fl_str_mv Nieto, Carla I.
Elguero, José
Acuña-Castroviejo, D.
author Nieto, Carla I.
author_facet Nieto, Carla I.
Elguero, José
Acuña-Castroviejo, D.
author_role author
author2 Elguero, José
Acuña-Castroviejo, D.
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas (España)
Universidad Nacional de Educación a Distancia (España)
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv NOS inhibitors
Crystallography
Curcumin
Fluorine derivatives
Multinuclear NMR
Pyrazoles
Tautomerism
topic NOS inhibitors
Crystallography
Curcumin
Fluorine derivatives
Multinuclear NMR
Pyrazoles
Tautomerism
description A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (H, C, F and N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1Hpyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/137193
url http://hdl.handle.net/10261/137193
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2014-56833-R
S2009/PPQ-1533/MADRISOLAR2
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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repository.mail.fl_str_mv
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