FLAVONOIDS AND ANTIMYCOTICS: A POSSIBILE SYNERGISTIC COMBINATION FOR THE TREATMENT OF CANDIDIASIS AND CRYPTOCOCCOSIS.

The treatment of candidiasis and cryptococcosis is based on the use of antimycotic drugs such as amphotericin B, 5-fluorocytosine, miconazole and fluconazole. Isoliquiritigenin is a member of the flavonoids and data in scientific literature assert that these compounds can modulate the biosynthesis of endogenous sterols, which are known to be very important for the survival of mycete. In this study we investigated the antifungal effect of isoliquiritigenin on strains of Candidae spp and C.neoformans cultured on Sabouraud medium. Amphotericin B, 5-fluorocytosine, miconazole and fluconazole were chosen as reference drugs. Sensitivity tests were performed in according with the NCCLS method for agar dilution and MIC values were calculated for all the substances. No antifungal activity was evident in cultures treated with isoliquiritigenin (MIC values >100mg/L) while, very interesting results came from the combination: isoliquiritigenin/ antifungal drugs used at inhibitory and sub-inhibitory concentrations on yeast cultures (isoliquiritigenin 50-10mg/L, amphotericin B 10-0.1mg/L, 5-fluorocytosine 2.5-0.5mg/L, miconazole 0.25-0.05, fluconazole10-0.1mg/L). The FIC index used to estimate the interactions outcomes was also calculated. The association of isoliquiritigenin with the antimycotic often resulted in a synergic effect with addition (0.55<FIC index<1). In few cases we observed indifference (1<FIC index<2). Antagonism never appeared. Finally, we performed the MTT test on Vero cells to evaluate the toxic effect of the dosages used in the combinations. The results from the MTT test performed on Vero coltures added with the drugs used alone or in association showed the low toxicity of the combinations.