RESUMO

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.

Assuntos

Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Farmacorresistência Fúngica/efeitos dos fármacos , Fluconazol/farmacologia , Naftoquinonas/farmacologia , Animais , Antifúngicos/síntese química , Antifúngicos/química , Candida/classificação , Candida/genética , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/genética , Candida tropicalis/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , DNA Fúngico/química , DNA Fúngico/genética , DNA Fúngico/metabolismo , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Químicos , Dados de Sequência Molecular , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Fosfatidilserinas , RNA Ribossômico 5,8S/genética , Espécies Reativas de Oxigênio/metabolismo , Análise de Sequência de DNA