Resumo

Studies have reported a notable increase of infections by non-albicans species corresponding to 36-63% of all cases. Among the invasive fungal infections, C. Tropicalis has been reported as a major non-albicans Candida species causing fungemia in patients. Reports show that this species is the second most commonly isolated Brazilian hospitals. This scenario can be explained by the high level of non-albicans species resistance to certain antifungal drugs, where clinical isolates of C. Tropicalis resistant to fluconazole (FLC) have been widely reported in the recent years. Naphthoquinoidal compounds have been attracted much interest in pharmaceutical field due the fact these compounds are considered privileged structures for the development of new drugs (as prototype) and their distintic biological properties. The aim of this study was to evaluate and compare the antifungal activity of three semisynthetic naphthofuranquinones molecules against C. Tropicalis strains resistant to FLC. For antifungal assay the broth microdilution susceptibility test was performed according to the document M27-A3. Cultured fungi were exposed to naphitoquinoidal drugs (0.125-64 &mi;g/mL) for 48 h. Also, flow cytometry procedures and modified comet assay were applied to analyze other parameters (i.e. membrane integrity, mitochondrial transmembrane potential, DNA damage, and oxidative stress) involved in anti-candida effects. The minimum inhibitory concentration showed antifungal activity against FLC-resistant C. Tropicalis. Additionally, the cytotoxicity of naphthofuranquinones caused damage of membrane, morphological changes, depolarization of the mitochondrial membrane, breaks of chains and oxidative damage to DNA. The results indicate that these natural products can be effective potential candidates for the development of new strategies to treat Candida infections.