Abstract The genus Candida represents the main cause of infections of fungal origin. Some species stand out as disease promoters in humans, such as C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. This study evaluated the antifungal effects of propyl (E)-3-(furan-2-yl) acrylate. The minimum inhibitory concentration of the synthetic compound, amphotericin B and fluconazole alone against four species of Candida ranged from 64 to 512 μg/mL, 1 to 2 μg/mL, and 32 to 256 μg/mL, respectively. The synergistic effect of the test substance was observed when associated with fluconazole against C. glabrata, there was no antagonism between the substances against any of the tested strains. The potential drug promoted morphological changes in C. albicans, decreasing the amount of resistance, virulence, and reproduction structures, such as the formation of pseudohyphae, blastoconidia, and chlamydospores, ensuring the antifungal potential of this substance. It was also possible to identify the fungicidal profile of the test substance through the study of the growth kinetics of C. albicans. Finally, it was observed that the test compound inhibited the ergosterol biosynthesis by yeast. origin humans C albicans glabrata parapsilosis tropicalis E3furan2yl Efuranyl E 3 furan yl (E)-3-(furan-2-yl acrylate 6 51 μgmL μg mL μg/mL 25 respectively strains resistance virulence structures pseudohyphae blastoconidia chlamydospores Finally yeast 5

RESUMEN El objetivo fue evaluar la actividad antifúngica del ibuprofeno solo y asociado con anfotericina B o ketoconazol contra especies de Candida. Se utilizaron cepas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei y C. parapsilosis. La concentración inhibitoria mínima (MIC) se determinó mediante el método de microdilución y el estudio de asociación fue realizado a través del ensayo de checkboard. La concentración de 512 μg/mL inhibió aproximadamente el 65% de las cepas analizadas, mientras 35% de las cepas presentaron valores de MIC superiores a 2048 μg/mL. Las asociaciones de ibuprofeno con anfotericina B contra C. tropicalis e ibuprofeno con ketoconazol contra C. krusei mostraron un efecto sinérgico. Se evidenciaron efectos antagonistas en la combinación de ibuprofeno con anfotericina B contra C. guilliermondii y C. albicans, así como en la asociación de ibuprofeno con ketoconazol contra C. albicans y C. tropicalis. Se descubrió, a través de los experimentos, que el ibuprofeno mostró actividad antifúngica contra la mayoría de las especies de Candida probadas. Las combinaciones de ibuprofeno y antifúngicos tuvieron efectos sinérgicos. Sin embargo, se evidenciaron resultados antagónicos en la asociación con ibuprofeno, lo que dificultaría la aplicabilidad clínica. Por lo tanto, los estudios de esta actividad combinada deben investigarse, considerando que esta asociación puede ser positiva para la terapia antimicótica.

SUMMARY The objective was evaluating the antifungal activity of ibuprofen alone and when associated with amphotericin B or ketoconazole against Candida species. Strains of C. albicans, C. tropicalis, C. guilliermondii, C. krusei and C. parapsilosis were used. The minimum inhibitory concentration (MIC) was determined by the microdilution method and the association study performed through the checkerboard assay. The concentration of 512 μg/mL inhibited approximately 65% of the tested strains, while against 35% of the strains presented MIC values above 2048 μg/mL. Associations of ibuprofen with amphotericin B against C. tropicalis and ibuprofen with ketoconazole against C. krusei showed synergistic effect. Antagonistic effects were evidenced in the combination of ibuprofen with amphotericin B against C. guilliermondii and C. albicans, as well as in the association of ibuprofen with ketoconazole against C. albicans and C. tropicalis. Through the experiments, it was found that ibuprofen showed antifungal activity against most of the Candida species tested. The combinations of ibuprofen and antifungals had synergistic effects. However, antagonistic results were evidenced in the association with ibuprofen, which would make clinical applicability difficult. Therefore, studies of this combined activity should be investigated, considering that this association may be positive for anti-fungal therapy.

RESUMO O objetivo do estudo foi avaliar a atividade antifúngica do ibuprofeno sozinho e quando associado com anfotericina B ou cetoconazol contra espécies de Candida. Foram utilizadas cepas fúngicas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei e C. parapsilosis, entre isolados clínicos e cepas padrão. A concentração inibitória mínima (CIM) foi determinada pela técnica de microdiluição e o estudo de associação realizado através do ensaio checkerboard. A concentração de 512 μg/mL foi capaz de inibir, aproximadamente, 65% das cepas ensaiadas, enquanto que 35% das estirpes apresentaram valores da CIM acima de 2048 μg/mL. Associações do ibuprofeno com anfotericina B contra C. tropicalis e ibuprofeno mais cetoconazol contra C. krusei mostraram efeito sinérgico. Efeitos antagônicos foram evidenciados na combinação do ibuprofeno com anfotericina B contra C. guilliermondii e C. albicans, como também na associação do ibuprofeno com cetoconazol contra C. albicans e C. tropicalis. Por meio dos experimentos, pôde-se afirmar que o ibuprofeno exerceu atividade antifúngica contra a maioria das espécies de Candida ensaiadas. Os efeitos das combinações entre o ibuprofeno e os antifúngicos promoveram efeitos sinérgicos. No entanto, resultados antagônicos foram evidenciados na associação com o ibuprofeno, o que dificultaria aplicabilidade clínica. Logo, estudos dessa atividade combinada devem ser investigados, pois esta associação pode traçar pontos positivos na terapia antifúngica.

Candida albicans is an opportunistic yeast and a member of the normal human flora that commonly causes infections in patients with any type of deficiency of the immune system. The essential oils have been tested for antimycotic activity and pose much potential as antifungal agents. This work investigated the activity of the essential oil of Cymbopogon winterianus against C. albicans by MIC, MFC and time-kill methods. The essential oil (EO) was obtained by hydrodistillation using a Clevenger-type apparatus. It was tested fifteen strains of C. albicans. The MIC was determined by the microdilution method and the MFC was determined when an aliquot of the broth microdilution was cultivated in SDA medium. The phytochemical analysis of EO showed presence of citronellal (23,59%), geraniol (18,81%) and citronellol (11,74%). The EO showed antifungal activity, and the concentrations 625 µg/mL and 1250 µg/mL inhibited the growth of all strains tested and it was fungicidal, respectively. The antimicrobial activity of various concentrations of EO was analyzed over time, it was found concentration-dependent antifungal activity, whose behavior was similar to amphotericin B and nystatin.