Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action

Autores
Carrasco, Héctor; Raimondi, Marcela Patricia; Svetaz, Laura Andrea; Di Liberto, Melina Gabriela; Rodriguez, María V.; Espinoza, Luis; Madrid, Alejandro; Zacchino, Susana Alicia Stella
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.
Fil: Carrasco, Héctor. Universidad Andrés Bello; Chile
Fil: Raimondi, Marcela Patricia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina
Fil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Di Liberto, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Rodriguez, María V.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Espinoza, Luis. Universidad Técnica Federico Santa María; Chile
Fil: Madrid, Alejandro. Universidad Técnica Federico Santa María; Chile
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Materia
EUGENOL DERIVATIVES
ANTIFUNGAL ACTIVITY
MECHANISM OF ANTIFUNGAL ACTION
LIPOPHILICITY
SAR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/268718
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/268718
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of ActionCarrasco, HéctorRaimondi, Marcela PatriciaSvetaz, Laura AndreaDi Liberto, Melina GabrielaRodriguez, María V.Espinoza, LuisMadrid, AlejandroZacchino, Susana Alicia StellaEUGENOL DERIVATIVESANTIFUNGAL ACTIVITYMECHANISM OF ANTIFUNGAL ACTIONLIPOPHILICITYSARhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.Fil: Carrasco, Héctor. Universidad Andrés Bello; ChileFil: Raimondi, Marcela Patricia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; ArgentinaFil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Di Liberto, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Rodriguez, María V.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaFil: Espinoza, Luis. Universidad Técnica Federico Santa María; ChileFil: Madrid, Alejandro. Universidad Técnica Federico Santa María; ChileFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaMolecular Diversity Preservation International2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/268718Carrasco, Héctor; Raimondi, Marcela Patricia; Svetaz, Laura Andrea; Di Liberto, Melina Gabriela; Rodriguez, María V.; et al.; Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action; Molecular Diversity Preservation International; Molecules; 17; 1; 1-2012; 1002-10241420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/17/1/1002info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules17011002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:11:25Zoai:ri.conicet.gov.ar:11336/268718instacron: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 10:11:25.791CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
title Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
spellingShingle Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
Carrasco, Héctor
EUGENOL DERIVATIVES
ANTIFUNGAL ACTIVITY
MECHANISM OF ANTIFUNGAL ACTION
LIPOPHILICITY
SAR
title_short Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
title_full Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
title_fullStr Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
title_full_unstemmed Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
title_sort Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action
dc.creator.none.fl_str_mv Carrasco, Héctor
Raimondi, Marcela Patricia
Svetaz, Laura Andrea
Di Liberto, Melina Gabriela
Rodriguez, María V.
Espinoza, Luis
Madrid, Alejandro
Zacchino, Susana Alicia Stella
author Carrasco, Héctor
author_facet Carrasco, Héctor
Raimondi, Marcela Patricia
Svetaz, Laura Andrea
Di Liberto, Melina Gabriela
Rodriguez, María V.
Espinoza, Luis
Madrid, Alejandro
Zacchino, Susana Alicia Stella
author_role author
author2 Raimondi, Marcela Patricia
Svetaz, Laura Andrea
Di Liberto, Melina Gabriela
Rodriguez, María V.
Espinoza, Luis
Madrid, Alejandro
Zacchino, Susana Alicia Stella
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EUGENOL DERIVATIVES
ANTIFUNGAL ACTIVITY
MECHANISM OF ANTIFUNGAL ACTION
LIPOPHILICITY
SAR
topic EUGENOL DERIVATIVES
ANTIFUNGAL ACTIVITY
MECHANISM OF ANTIFUNGAL ACTION
LIPOPHILICITY
SAR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.
Fil: Carrasco, Héctor. Universidad Andrés Bello; Chile
Fil: Raimondi, Marcela Patricia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Microbiología; Argentina
Fil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Di Liberto, Melina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Rodriguez, María V.. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Fil: Espinoza, Luis. Universidad Técnica Federico Santa María; Chile
Fil: Madrid, Alejandro. Universidad Técnica Federico Santa María; Chile
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
description Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/268718
Carrasco, Héctor; Raimondi, Marcela Patricia; Svetaz, Laura Andrea; Di Liberto, Melina Gabriela; Rodriguez, María V.; et al.; Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action; Molecular Diversity Preservation International; Molecules; 17; 1; 1-2012; 1002-1024
1420-3049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/268718
identifier_str_mv Carrasco, Héctor; Raimondi, Marcela Patricia; Svetaz, Laura Andrea; Di Liberto, Melina Gabriela; Rodriguez, María V.; et al.; Antifungal Activity of Eugenol Analogues: Influence of Different Substituents and Studies on Mechanism of Action; Molecular Diversity Preservation International; Molecules; 17; 1; 1-2012; 1002-1024
1420-3049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1420-3049/17/1/1002
info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules17011002
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
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: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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