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PLoS One ; 9(5): e93698, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24817320

RESUMEN

In recent decades, the incidence of candidemia in tertiary hospitals worldwide has substantially increased. These infections are a major cause of morbidity and mortality; in addition, they prolong hospital stays and raise the costs associated with treatment. Studies have reported a significant increase in infections by non-albicans Candida species, especially C. tropicalis. The number of antifungal drugs on the market is small in comparison to the number of antibacterial agents available. The limited number of treatment options, coupled with the increasing frequency of cross-resistance, makes it necessary to develop new therapeutic strategies. The objective of this study was to evaluate and compare the antifungal activities of three semisynthetic naphthofuranquinone molecules against fluconazole-resistant Candida spp. strains. These results allowed to us to evaluate the antifungal effects of three naphthofuranquinones on fluconazole-resistant C. tropicalis. The toxicity of these compounds was manifested as increased intracellular ROS, which resulted in membrane damage and changes in cell size/granularity, mitochondrial membrane depolarization, and DNA damage (including oxidation and strand breakage). In conclusion, the tested naphthofuranquinones (compounds 1-3) exhibited in vitro cytotoxicity against fluconazole-resistant Candida spp. strains.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Farmacorresistencia Fúngica/efectos de los fármacos , Fluconazol/farmacología , Naftoquinonas/farmacología , Animales , Antifúngicos/síntesis química , Antifúngicos/química , Candida/clasificación , Candida/genética , Candida tropicalis/efectos de los fármacos , Candida tropicalis/genética , Candida tropicalis/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Daño del ADN , ADN de Hongos/química , ADN de Hongos/genética , ADN de Hongos/metabolismo , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Datos de Secuencia Molecular , Estructura Molecular , Naftoquinonas/síntesis química , Naftoquinonas/química , Fosfatidilserinas , ARN Ribosómico 5.8S/genética , Especies Reactivas de Oxígeno/metabolismo , Análisis de Secuencia de ADN
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