IMBIV   05474
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA VEGETAL
Unidad Ejecutora - UE
artículos
Título:
Interactions of a prenylated flavonoid from Dalea elegans with fluconazole against azole- resistant Candida albicans.
Autor/es:
JOSÉ LUIS CABRERA; SOLEDAD FINCK; SEBASTIÁN BARCELÓ; ROBERTO A. DIEZ; MAXIMILIANO CALISE; CRISTINA PÉREZ; GABRIELA ORTEGA; MARIANA PERALTA
Revista:
PHYTOMEDICINE
Editorial:
ELSEVIER GMBH
Referencias:
Año: 2017 vol. 32 p. 24 - 29
ISSN:
0944-7113
Resumen:
AbstractBACKGROUND: The prenylated flavonoid 2´, 4´-dihydroxy-5´-(1´″, 1´″-dimethylallyl)-8-prenylpinocembrin (8PP, formerly 6PP) shows antifungal activity, inhibits rhodamine 6G efflux and reverses fluconazole (FCZ) resistance in azole-resistant Candida albicans overexpressing cdr1, cdr2 and mdr1 transporters.PURPOSE AND DESIGN: In this paper, we tried to characterize 8PP in vitro interactions on the cell growth and lethality of C. albicans. We also initiated preliminary in vivo toxicological studies on mice.METHODS:The effects of 8PP and FCZ on cell growth and viability of C. albicans were evaluated by CLSI guidelines. The checkerboard assay was used to search for interactions on cell growth. The time-kill assay was used to study fungicidal effects. Acute toxicity was evaluated at a single dose schedules.RESULTS: From the checkerboard design, and using a starting inoculum of 103CFU/ml, the fractional inhibitory concentration (FIC) of FCZ and 8PP could be determined as 0.11 and 0.50, respectively, with a FIC index value (FICI) of 0.61. This FICI and the isobologram showing a concave shape suggests an additive interaction between them. At a higher starting inoculum (105CFU/ml), C. albicans growth and viability were decreased by FCZ, 8PP and their combination in a concentration-dependent way. For FCZ, minimum fungicidal concentration (MFC) and FC50 (the concentration that kills 50% of the fungal cells) were 4-fold reduced (280-70µM) in combination with 125µM 8PP. A decrease of 3 log units in viable counts with respect to control was reached (3.65 ± 1.05 ?, p