RESUMO
Candidiasis is an opportunistic fungal infection with Candida albicans being the most frequently isolated species. Treatment of these infections is challenging due to resistance that can develop during therapy, and the limited number of available antifungal compounds. Given this situation, the aim of this study was to evaluate the antifungal activity of four thiazolylhydrazone compounds against C. albicans. Thiazolylhydrazone compounds 1, 2, 3, and 4 were found to exert antifungal activity, with MICs of 0.125â»16.0 µg/mL against C. albicans. The toxicity of the compounds was evaluated using human erythrocytes and yielded LC50 > 64 µg/mL. The compounds were further evaluated using the greater wax moth Galleria mellonella as an in vivo model. The compounds prolonged larval survival when tested between 5 and 15 mg/kg, performing as well as fluconazole. Compound 2 was evaluated in murine models of oral and systemic candidiasis. In the oral model, compound 2 reduced the fungal load on the mouse tongue; and in the systemic model it reduced the fungal burden found in the kidney when tested at 10 mg/kg. These results show that thiazolylhydrazones are an antifungal towards C. albicans with in vivo efficacy.
RESUMO
OBJECTIVES: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C. albicans. METHODS: The in vitro activity of PMC was evaluated against C. albicans. Additionally, an invertebrate infection model in Caenorhabditis elegans as well as two infected murine models of oral and systemic candidiasis were used to determine the antifungal efficacy of PMC in vivo. RESULTS: Minimum inhibitory concentrations (MICs) of PMC ranged from 4-32µg/mL against nine clinical and two reference C. albicans isolates. Interestingly, PMC inhibited filamentation in vitro at subinhibitory concentrations similar to fluconazole. PMC also showed low toxicity against murine macrophages and human erythrocytes. In the invertebrate infection model, PMC was efficient in prolonging survival of C. elegans infected with C. albicans SC5314. Treatment with PMC was efficient both in murine models of systemic and oral candidiasis and was similar to that observed with conventional drug treatments (nystatin and fluconazole). CONCLUSIONS: The results of this study indicate the therapeutic potential of PMC as it was able to inhibit filamentation of C. albicans in vitro. These alterations to the fungi by PMC resulted in a reduction of oral and systemic infection in mice. In conclusion, we present promising evidence of the anticandidal activity of PMC in vitro and in vivo.
Assuntos
Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Cicloexanonas/síntese química , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Caenorhabditis elegans , Cicloexanonas/química , Cicloexanonas/farmacologia , Modelos Animais de Doenças , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Fluconazol/farmacologia , Humanos , Camundongos , Testes de Sensibilidade MicrobianaRESUMO
A baixa oferta de mudas sadias e com qualidade tem sido um obstáculo para o crescimento da abacaxicultura no Brasil. A pesquisa foi realizada com o objetivo de avaliar a associação micorrízica, o crescimento e absorção de nutrientes em mudas micropropagadas de abacaxizeiro Imperial inoculadas com o fungo Piriformospora indica em cultivo com a aplicação de herbicidas. Foi utilizado o esquema fatorial 2 x 4, sendo os fatores duas inoculações: mudas inoculadas com o fungo P. indica e sem inoculação e quatro doses de herbicidas: 0; 1,5; 3,0 e 6,0 L ha-1 para o ametryn, 0; 1,6; 3,2; 6,4 L ha-1 para o diuron e 0; 0,4; 0,8 e 1,6 L ha-1 para o sulfametrazone, distribuídos no delineamento inteiramente casualizado, com três repetições. As doses dos herbicidas foram aplicadas ao substrato antes do plantio das mudas. A inoculação com o fungo P. indica foi feita no momento do plantio, colocando-se no substrato discos de micélio de 5 mm, contendo estruturas fúngicas. Aos 150 dias após a inoculação foi feita a análise da colonização micorrízica, dos teores de N, P e K e do crescimento das mudas. Os dados foram submetidos à análise de variância, regressão polinomial e comparação de médias, a 5% de probabilidade. Foi observada a associação do fungo P. indica com as mudas de abacaxizeiro Imperial com a aplicação de todos os herbicidas. As mudas associadas com o fungo apresentaram maiores...(AU)
The low supply of healthy and quality nursery plants has been an obstacle to the growth of pineapple crop in Brazil. The research was carried out with the aim of evaluating mycorrhizal association, growth and nutrient uptake of Imperial micropropagated pineapple plants inoculated with the fungus Piriformospora indica in cultivation with herbicide application. The 2 x 4 factorial scheme was used, being the factors the two inoculations: inoculated nursery plants with the fungus P. indica and without inoculation and four doses of herbicides: 0, 1.5, 3.0 and 6.0 L ha-1 for ametryn, 0, 1.6, 3.2, 6.4 L ha-1 for diuron and 0, 0.4, 0.8 and 1.6 L ha-1 for sulfametrazone distributed in a completely randomized design with three replications. The doses of herbicides were applied to substrate before planting. The inoculation with the fungus P. indica was made at the time of planting, placing in the substrate 5 mm mycelial discs containing fungal structures. At 150 days after inoculation evaluations were made by analysis of colonization, determination of N, P and K levels and of nursery plants growth. Data were subjected to analysis of variance and regression. The association of fungus P. indica with Imperial pineapple nursery plants was observed with the application of all herbicides. Imperial pineapple nursery plants associated with P. indica fungus showed higher levels of nutrients...(AU)
Assuntos
Ananas/crescimento & desenvolvimento , Ananas/parasitologia , Herbicidas/administração & dosagem , MicorrizasRESUMO
A baixa oferta de mudas sadias e com qualidade tem sido um obstáculo para o crescimento da abacaxicultura no Brasil. A pesquisa foi realizada com o objetivo de avaliar a associação micorrízica, o crescimento e absorção de nutrientes em mudas micropropagadas de abacaxizeiro Imperial inoculadas com o fungo Piriformospora indica em cultivo com a aplicação de herbicidas. Foi utilizado o esquema fatorial 2 x 4, sendo os fatores duas inoculações: mudas inoculadas com o fungo P. indica e sem inoculação e quatro doses de herbicidas: 0; 1,5; 3,0 e 6,0 L ha-1 para o ametryn, 0; 1,6; 3,2; 6,4 L ha-1 para o diuron e 0; 0,4; 0,8 e 1,6 L ha-1 para o sulfametrazone, distribuídos no delineamento inteiramente casualizado, com três repetições. As doses dos herbicidas foram aplicadas ao substrato antes do plantio das mudas. A inoculação com o fungo P. indica foi feita no momento do plantio, colocando-se no substrato discos de micélio de 5 mm, contendo estruturas fúngicas. Aos 150 dias após a inoculação foi feita a análise da colonização micorrízica, dos teores de N, P e K e do crescimento das mudas. Os dados foram submetidos à análise de variância, regressão polinomial e comparação de médias, a 5% de probabilidade. Foi observada a associação do fungo P. indica com as mudas de abacaxizeiro Imperial com a aplicação de todos os herbicidas. As mudas associadas com o fungo apresentaram maiores...
The low supply of healthy and quality nursery plants has been an obstacle to the growth of pineapple crop in Brazil. The research was carried out with the aim of evaluating mycorrhizal association, growth and nutrient uptake of Imperial micropropagated pineapple plants inoculated with the fungus Piriformospora indica in cultivation with herbicide application. The 2 x 4 factorial scheme was used, being the factors the two inoculations: inoculated nursery plants with the fungus P. indica and without inoculation and four doses of herbicides: 0, 1.5, 3.0 and 6.0 L ha-1 for ametryn, 0, 1.6, 3.2, 6.4 L ha-1 for diuron and 0, 0.4, 0.8 and 1.6 L ha-1 for sulfametrazone distributed in a completely randomized design with three replications. The doses of herbicides were applied to substrate before planting. The inoculation with the fungus P. indica was made at the time of planting, placing in the substrate 5 mm mycelial discs containing fungal structures. At 150 days after inoculation evaluations were made by analysis of colonization, determination of N, P and K levels and of nursery plants growth. Data were subjected to analysis of variance and regression. The association of fungus P. indica with Imperial pineapple nursery plants was observed with the application of all herbicides. Imperial pineapple nursery plants associated with P. indica fungus showed higher levels of nutrients...