albicans (78) C. albicans (ATCC 90028) C. albicans (78) C. albicans (ATCC 90028) Gomesin 5.5 11 – - Fluconazole * 186 – - Gomesin + Fluconazole 0.6 + 3.5 1.3 + 14.3 0.11 0.19 * = not detected in up to 1.5 mM Evaluation of the antifungal activity of gomesin in mice with disseminated and Sirolimus clinical trial vaginal candidiasis Treatment with 5 mg/kg and 15 mg/kg of gomesin in mice with disseminated candidiasis effectively reduced the fungal burden of the kidneys, spleen and liver when compared with the control group (PBS-treated mice) (Figure 1A-C). Treatment with 10 mg/kg and 20 mg/kg of fluconazole also effectively controlled the infection (Figure 1A-C). Moreover,

treatment of vaginal candidiasis with

0.2% and 0.5% gomesin and 2% miconazole showed a significant decrease in colony forming units (CFUs) when compared with vehicle treatment (control group) (Figure 1D). The combination of gomesin and fluconazole or miconazole did not result in a synergistic effect. Figure 1 Gomesin treatment of mice infected with C. albicans. Evaluation of the number of colony forming units (CFU) per gram of tissue of the kidneys (A), spleen (B), liver (C) and vagina (D). The disseminated candidiasis was performed check details by intravenous injection of 3 × 105 yeasts suspended in 100 μL of PBS and vaginal candidiasis was performed by inoculating 3 × 106 yeasts suspended in 20 μL of PBS. The treatment was done one, three and six days after infection with C. albicans (strain 78). Animals were treated with different doses of gomesin (GOM), fluconazole (FLUCO) and miconazole (MICO). As Chlormezanone a control, infected animals received only PBS or cream (CREAM). * Indicates statistical significance (ANOVA with post-Tukey test, P < 0.05). Cytokine levels in kidneys of gomesin-treated mice Treatment with gomesin and fluconazole significantly increased the concentration of TNF-α, IFN-γ and IL-6 in the kidneys compared

to controls that were not infected and not treated as well as controls that were infected and treated with PBS (Figure 2). Figure 2 Cytokine levels in kidneys. Cytokine levels were evaluated in the kidneys of mice treated with gomesin (5 mg/kg) and fluconazole (20 mg/kg). Non-infected and untreated animals (NINF), as well as infected animals that received PBS, were used as controls. * Indicates statistical significance (t-test, P < 0.05) compared to the control INF. Evaluation of the effect of antifungal drugs in immunosuppressed mice with disseminated candidiasis The group of infected animals that received PBS (control) reached 100% mortality on the fifteenth day after infection. No statistically significant difference was observed between the group treated with gomesin (5 mg/kg) and the group treated with fluconazole (20 mg/kg), although there was an increase in survival during the last treatment.