Anthraquinones against : antifungal interaction, biofilm inhibition and pathogenicity in the model.

Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of . Anthraquinones and antifungals are associated with preventing biofilm formation and disrupting these communities. Antraquinones reduced the pathogenicity in the model. This study aimed to evaluate the interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of . Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. pathogenicity was investigated using the nematode . Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against biofilms. The mortality rate reached 76.7 % after the worms were exposed to for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to and these compounds at same time. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.