A PRENYLATED FLAVONOID ENHANCES THE EFFECT OF FLUCONAZOLE ON VIABILITY OF RESISTANT Candida albicans

PERALTA MARIANA A; BARCELÓ SEBATIÁN N; FINCK SOLEDAD; ORTEGA, M. GABRIELA; DIEZ, ROBERTO; CABRERA JOSE L.; PEREZ, CRISTINA

Córdoba

Congreso; 3° Reunión Internacional de Ciencias Farmacéuticas; 2014

Facultad de Ciencias Químicas, U.N.C

The prenylated flavanone 2',4'-dihydroxy-5'-(1''',1'''-dimethylallyl)-8-prenylpinocembrin (1) from Dalea elegans Gillies ex Hook et Arn. showed antimicrobial properties and inhibition of fluconazole transport in resistant Candida albicans (RCa) overexpressing Cdr1p, Cdr2p and Mdr1p pumps. Moreover this compound restores fluconazole efficacy. In this work we study the effect of 1 and fluconazole on viability of RCa. Compound 1 was isolated from D. elegans roots. Microorganism: An azole-resistant C. albicans isolated from the oral cavity and overexpressing transporter genes was used. Cell viability of C. albicans was evaluated as previously described. A 105 CFU/ml starting inoculum was cultured in a microtiter 96-well plate at 37°C. Variable concentrations of 1, fluconazole, or their combinations were used. Absorbance was measured at 540nm. Each sample was further serially diluted and cultured on Sabouraud agar plates. CFU/ml were counted after 24 h of incubation at 37°C. At 125µM compound 1 and its combination with equal concentration of fluconazole significantly reduced cell viability (CFU/ml). Survival values (? of control) were: 629±71; 979±124 and 285±108 for 1, fluconazole and the combination, respectively. By combining fluconazole with 125μM of 1, survival was reduced in a concentration dependent way. With 1000µM fluconazole, viability was reduced in 3-log (3.3±1.6) with respect to control (1000 ?), reaching values close to a fungicide effect. In fungal growth evaluation, starting from a 105 CFU/ml inoculum, the combination of fluconazole and 1 was more effective inhibiting the growth of RCa. In fact, inhibitory concentration 50 (IC50) of compounds alone were 1750 and 250µM of fluconazole and 1, respectively while the same inhibition was achieved by combining fractions of them (1/2 fluconazole IC50 with 1/7 compound 1 IC50). The two compounds combined are more potent in inhibiting the growth of RCa that each compound separately. The combination of both fungistatic compounds at their MIC produced values of survival close to fungicidal effect.