A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans

Autores
Peralta, Mariana Andrea; Calise, Maximiliano; Fornari, M. Cecilia; Ortega, María Gabriela; Diez, Roberto A.; Cabrera, Jose Luis; Perez, Cristina
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In previous studies, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12–99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12–99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12–99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.
Fil: Peralta, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Calise, Maximiliano. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Fornari, M. Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Diez, Roberto A.. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Perez, Cristina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
Materia
Prenylated Flavonoid
Dalea Elegans
Fabaceae
Rhodamine Efflux Inhibition
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:11336/15846
Acceder
id CONICETDig_75cbaa25eb1d8e15eb48d5135ee0c609
oai_identifier_str oai:ri.conicet.gov.ar:11336/15846
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicansPeralta, Mariana AndreaCalise, MaximilianoFornari, M. CeciliaOrtega, María GabrielaDiez, Roberto A.Cabrera, Jose LuisPerez, CristinaPrenylated FlavonoidDalea ElegansFabaceaeRhodamine Efflux Inhibitionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In previous studies, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12–99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12–99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12–99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.Fil: Peralta, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Calise, Maximiliano. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Fornari, M. Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Diez, Roberto A.. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Perez, Cristina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; ArgentinaGeorg Thieme Verlag Kg2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15846Peralta, Mariana Andrea; Calise, Maximiliano; Fornari, M. Cecilia; Ortega, María Gabriela; Diez, Roberto A.; et al.; A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans; Georg Thieme Verlag Kg; Planta Medica; 78; 10; 5-2012; 981-9870032-0943enginfo:eu-repo/semantics/altIdentifier/doi/10.1055/s-0031-1298627info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/DOI/DOI?10.1055/s-0031-1298627info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:28:13Zoai:ri.conicet.gov.ar:11336/15846instacron: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:34982025-10-15 15:28:14.014CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
title A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
spellingShingle A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
Peralta, Mariana Andrea
Prenylated Flavonoid
Dalea Elegans
Fabaceae
Rhodamine Efflux Inhibition
title_short A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
title_full A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
title_fullStr A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
title_full_unstemmed A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
title_sort A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans
dc.creator.none.fl_str_mv Peralta, Mariana Andrea
Calise, Maximiliano
Fornari, M. Cecilia
Ortega, María Gabriela
Diez, Roberto A.
Cabrera, Jose Luis
Perez, Cristina
author Peralta, Mariana Andrea
author_facet Peralta, Mariana Andrea
Calise, Maximiliano
Fornari, M. Cecilia
Ortega, María Gabriela
Diez, Roberto A.
Cabrera, Jose Luis
Perez, Cristina
author_role author
author2 Calise, Maximiliano
Fornari, M. Cecilia
Ortega, María Gabriela
Diez, Roberto A.
Cabrera, Jose Luis
Perez, Cristina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Prenylated Flavonoid
Dalea Elegans
Fabaceae
Rhodamine Efflux Inhibition
topic Prenylated Flavonoid
Dalea Elegans
Fabaceae
Rhodamine Efflux Inhibition
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In previous studies, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12–99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12–99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12–99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.
Fil: Peralta, Mariana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Calise, Maximiliano. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Fornari, M. Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Ortega, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Diez, Roberto A.. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Cabrera, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina
Fil: Perez, Cristina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Farmacología; Argentina
description In previous studies, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, a prenylated flavonoid isolated from Dalea elegans roots, showed activity against multiresistant Staphylococcus aureus and Candida albicans, as well as an uncoupling effect on mitochondria and antioxidant activity. The aim of this study was to evaluate the inhibitory effects of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and fluconazole on the efflux of rhodamine 6 G in azole-resistant C. albicans 12–99 that expresses multidrug transporters Cdr1p, Cdr2p, and Mdr1p. The effect of fluconazole and 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin on rhodamine 6 G efflux was assessed in both azole-sensitive and azole-resistant C. albicans. Between 1 and 1000 µM, 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin inhibited rhodamine 6 G efflux only in azole-resistant C. albicans 12–99 in a concentration-dependent manner (IC50 = 119 µM); a competitive effect was observed. It also showed selectivity of action in comparison with other flavanones (6-prenylpinocembrin, isolated from aerial parts of D. elegans, pinocembrin, naringenin, and hesperetin, all at 250 µM). To check the possible implications of the inhibition of azole efflux on cell growth, antifungal assays were conducted. Minimal inhibitory concentration values were 150 µM for 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin and higher than 400 µM for fluconazole. The combination of both compounds at either inhibitory or subinhibitory concentrations was significantly more effective than each compound separately. Minimal inhibitory concentration for fluconazole decreased by more than 400 times in the presence of 100 µM 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin, reversing azole resistance and giving values similar to those of azole-sensitive C. albicans. These data are consistent with a dual action of 2′,4′-dihydroxy-5′-(1′′′,1′′′-dimethylallyl)-6-prenylpinocembrin: direct antifungal effect on azole-resistant C. albicans 12–99 and inhibition of azole transporters, which results in reversion of fluconazole resistance.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
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/11336/15846
Peralta, Mariana Andrea; Calise, Maximiliano; Fornari, M. Cecilia; Ortega, María Gabriela; Diez, Roberto A.; et al.; A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans; Georg Thieme Verlag Kg; Planta Medica; 78; 10; 5-2012; 981-987
0032-0943
url http://hdl.handle.net/11336/15846
identifier_str_mv Peralta, Mariana Andrea; Calise, Maximiliano; Fornari, M. Cecilia; Ortega, María Gabriela; Diez, Roberto A.; et al.; A Prenylated Flavanone from Dalea elegans Inhibits Rhodamine 6 G Efflux and Reverses FluconazoleResistance in Candida albicans; Georg Thieme Verlag Kg; Planta Medica; 78; 10; 5-2012; 981-987
0032-0943
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1055/s-0031-1298627
info:eu-repo/semantics/altIdentifier/url/https://www.thieme-connect.de/DOI/DOI?10.1055/s-0031-1298627
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Georg Thieme Verlag Kg
publisher.none.fl_str_mv Georg Thieme Verlag Kg
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
_version_ 1846083423140052992
score 13.22299

Publicaciones similares