N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity

Autores
Sarmiento, Gabriela Pabla; Martini, María Florencia; Vitale, Roxana Gabriela; Fabian, Lucas Emanuel; Afeltra, Javier; Vega, Daniel; Moltrasio, Graciela Yolanda; Moglioni, Albertina Gladys
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A serie of N-acetyl phenothiazines and related compounds was synthesized by means of the acetylation reaction of the corresponding phenothiazine with the appropriate reagent using microwave irradiation. Structural elucidation of these heterocyclic derivatives was done using 1 H, 13C NMR spectra. The equilibra between conformationals enantiomers were studied as a possible atropisomerism case. The single crystal X-ray diffraction of some derivatives was also recorded and the presence of enantiomers could be confirmed. The antifungal activity evaluation of all N-acetyl phenothiazines prepared by us in this and in a previous work, was performed in vitro against 163 isolated human pathogenic yeasts and filamentous fungi, including: Cryptococcus neoformans, Candida albicans, Candida non-albicans, Aspergillus and Acremonium-Fusarium. The most promising compounds were those bearing one chlorine or bromine atom attached to the N-acetyl group. These compounds were as active as 5-fluorocitosine (5-FC) or fluconazole (FCZ), currently in clinical use. A structure-activity relationship (SAR) and a quantitative structure-activity relationship (QSAR) for antifungal activity of each genus were established.
Fil: Sarmiento, Gabriela Pabla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Vitale, Roxana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Afeltra, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Vega, Daniel. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Moltrasio, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Materia
N-acetyl phenothiazines
Microwave assisted synthesis
Human pathogenic yeasts
Filamentous fungi
Conformational isomers
QSAR
X-ray diffraction
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:11336/47834
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47834
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activitySarmiento, Gabriela PablaMartini, María FlorenciaVitale, Roxana GabrielaFabian, Lucas EmanuelAfeltra, JavierVega, DanielMoltrasio, Graciela YolandaMoglioni, Albertina GladysN-acetyl phenothiazinesMicrowave assisted synthesisHuman pathogenic yeastsFilamentous fungiConformational isomersQSARX-ray diffractionhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A serie of N-acetyl phenothiazines and related compounds was synthesized by means of the acetylation reaction of the corresponding phenothiazine with the appropriate reagent using microwave irradiation. Structural elucidation of these heterocyclic derivatives was done using 1 H, 13C NMR spectra. The equilibra between conformationals enantiomers were studied as a possible atropisomerism case. The single crystal X-ray diffraction of some derivatives was also recorded and the presence of enantiomers could be confirmed. The antifungal activity evaluation of all N-acetyl phenothiazines prepared by us in this and in a previous work, was performed in vitro against 163 isolated human pathogenic yeasts and filamentous fungi, including: Cryptococcus neoformans, Candida albicans, Candida non-albicans, Aspergillus and Acremonium-Fusarium. The most promising compounds were those bearing one chlorine or bromine atom attached to the N-acetyl group. These compounds were as active as 5-fluorocitosine (5-FC) or fluconazole (FCZ), currently in clinical use. A structure-activity relationship (SAR) and a quantitative structure-activity relationship (QSAR) for antifungal activity of each genus were established.Fil: Sarmiento, Gabriela Pabla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Vitale, Roxana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Afeltra, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Vega, Daniel. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Moltrasio, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaElsevier2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47834Sarmiento, Gabriela Pabla; Martini, María Florencia; Vitale, Roxana Gabriela; Fabian, Lucas Emanuel; Afeltra, Javier; et al.; N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity; Elsevier; Arabian Journal of Chemistry; 12-2017; 1-121878-5352CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.arabjc.2017.11.019info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1878535217302344info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:19Zoai:ri.conicet.gov.ar:11336/47834instacron: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 09:50:19.708CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
title N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
spellingShingle N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
Sarmiento, Gabriela Pabla
N-acetyl phenothiazines
Microwave assisted synthesis
Human pathogenic yeasts
Filamentous fungi
Conformational isomers
QSAR
X-ray diffraction
title_short N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
title_full N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
title_fullStr N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
title_full_unstemmed N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
title_sort N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity
dc.creator.none.fl_str_mv Sarmiento, Gabriela Pabla
Martini, María Florencia
Vitale, Roxana Gabriela
Fabian, Lucas Emanuel
Afeltra, Javier
Vega, Daniel
Moltrasio, Graciela Yolanda
Moglioni, Albertina Gladys
author Sarmiento, Gabriela Pabla
author_facet Sarmiento, Gabriela Pabla
Martini, María Florencia
Vitale, Roxana Gabriela
Fabian, Lucas Emanuel
Afeltra, Javier
Vega, Daniel
Moltrasio, Graciela Yolanda
Moglioni, Albertina Gladys
author_role author
author2 Martini, María Florencia
Vitale, Roxana Gabriela
Fabian, Lucas Emanuel
Afeltra, Javier
Vega, Daniel
Moltrasio, Graciela Yolanda
Moglioni, Albertina Gladys
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv N-acetyl phenothiazines
Microwave assisted synthesis
Human pathogenic yeasts
Filamentous fungi
Conformational isomers
QSAR
X-ray diffraction
topic N-acetyl phenothiazines
Microwave assisted synthesis
Human pathogenic yeasts
Filamentous fungi
Conformational isomers
QSAR
X-ray diffraction
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A serie of N-acetyl phenothiazines and related compounds was synthesized by means of the acetylation reaction of the corresponding phenothiazine with the appropriate reagent using microwave irradiation. Structural elucidation of these heterocyclic derivatives was done using 1 H, 13C NMR spectra. The equilibra between conformationals enantiomers were studied as a possible atropisomerism case. The single crystal X-ray diffraction of some derivatives was also recorded and the presence of enantiomers could be confirmed. The antifungal activity evaluation of all N-acetyl phenothiazines prepared by us in this and in a previous work, was performed in vitro against 163 isolated human pathogenic yeasts and filamentous fungi, including: Cryptococcus neoformans, Candida albicans, Candida non-albicans, Aspergillus and Acremonium-Fusarium. The most promising compounds were those bearing one chlorine or bromine atom attached to the N-acetyl group. These compounds were as active as 5-fluorocitosine (5-FC) or fluconazole (FCZ), currently in clinical use. A structure-activity relationship (SAR) and a quantitative structure-activity relationship (QSAR) for antifungal activity of each genus were established.
Fil: Sarmiento, Gabriela Pabla. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Martini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Vitale, Roxana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Fabian, Lucas Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Afeltra, Javier. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; Argentina
Fil: Vega, Daniel. Comisión Nacional de Energía Atómica; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Moltrasio, Graciela Yolanda. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
description A serie of N-acetyl phenothiazines and related compounds was synthesized by means of the acetylation reaction of the corresponding phenothiazine with the appropriate reagent using microwave irradiation. Structural elucidation of these heterocyclic derivatives was done using 1 H, 13C NMR spectra. The equilibra between conformationals enantiomers were studied as a possible atropisomerism case. The single crystal X-ray diffraction of some derivatives was also recorded and the presence of enantiomers could be confirmed. The antifungal activity evaluation of all N-acetyl phenothiazines prepared by us in this and in a previous work, was performed in vitro against 163 isolated human pathogenic yeasts and filamentous fungi, including: Cryptococcus neoformans, Candida albicans, Candida non-albicans, Aspergillus and Acremonium-Fusarium. The most promising compounds were those bearing one chlorine or bromine atom attached to the N-acetyl group. These compounds were as active as 5-fluorocitosine (5-FC) or fluconazole (FCZ), currently in clinical use. A structure-activity relationship (SAR) and a quantitative structure-activity relationship (QSAR) for antifungal activity of each genus were established.
publishDate 2017
dc.date.none.fl_str_mv 2017-12
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/11336/47834
Sarmiento, Gabriela Pabla; Martini, María Florencia; Vitale, Roxana Gabriela; Fabian, Lucas Emanuel; Afeltra, Javier; et al.; N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity; Elsevier; Arabian Journal of Chemistry; 12-2017; 1-12
1878-5352
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47834
identifier_str_mv Sarmiento, Gabriela Pabla; Martini, María Florencia; Vitale, Roxana Gabriela; Fabian, Lucas Emanuel; Afeltra, Javier; et al.; N -haloacetyl phenothiazines and derivatives: Preparation, characterization and structure-activity relationship for antifungal activity; Elsevier; Arabian Journal of Chemistry; 12-2017; 1-12
1878-5352
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.arabjc.2017.11.019
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1878535217302344
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 Elsevier
publisher.none.fl_str_mv Elsevier
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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