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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 ((1)H, (13)C, (19)F...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332466/ https://www.ncbi.nlm.nih.gov/pubmed/26343623 http://dx.doi.org/10.3390/molecules200915643 |
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author | Nieto, Carla I. Cabildo, María Pilar Cornago, María Pilar Sanz, Dionisia Claramunt, Rosa M. Torralba, María Carmen Torres, María Rosario Elguero, José García, José A. López, Ana Acuña-Castroviejo, Darío |
author_facet | Nieto, Carla I. Cabildo, María Pilar Cornago, María Pilar Sanz, Dionisia Claramunt, Rosa M. Torralba, María Carmen Torres, María Rosario Elguero, José García, José A. López, Ana Acuña-Castroviejo, Darío |
author_sort | Nieto, Carla I. |
collection | PubMed |
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 ((1)H, (13)C, (19)F and (15)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-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms. |
format | Online Article Text |
id | pubmed-6332466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63324662019-01-24 Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin Nieto, Carla I. Cabildo, María Pilar Cornago, María Pilar Sanz, Dionisia Claramunt, Rosa M. Torralba, María Carmen Torres, María Rosario Elguero, José García, José A. López, Ana Acuña-Castroviejo, Darío Molecules Article 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 ((1)H, (13)C, (19)F and (15)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-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms. MDPI 2015-08-28 /pmc/articles/PMC6332466/ /pubmed/26343623 http://dx.doi.org/10.3390/molecules200915643 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nieto, Carla I. Cabildo, María Pilar Cornago, María Pilar Sanz, Dionisia Claramunt, Rosa M. Torralba, María Carmen Torres, María Rosario Elguero, José García, José A. López, Ana Acuña-Castroviejo, Darío Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin |
title | 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_short | Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin |
title_sort | fluorination effects on nos inhibitory activity of pyrazoles related to curcumin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332466/ https://www.ncbi.nlm.nih.gov/pubmed/26343623 http://dx.doi.org/10.3390/molecules200915643 |
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