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

Authors
Peralta, Mariana Andrea; Calise, Maximiliano; Fornari, M. Cecilia; Ortega, María Gabriela; Diez, Roberto A.; Cabrera, Jose Luis; Perez, Cristina
Publication Year
2012
Language
English
Format
article
Status
Published version
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.
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
Subject
Prenylated flavonoid
Dalea elegans
Fabaceae
Rhodamine efflux inhibition
Otras Ciencias Biológicas
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/15846