Antifungal Activity of Naphthoquinoidal Compounds In Vitro against Fluconazole-Resistant Strains of Different Candida Species: A Special Emphasis on Mechanisms of Action on Candida tropicalis

作者：Neto Joao B A; da Silva Cecilia R; Neta Maria A S; Campos Rosana S; Siebra Janaina T; Silva Rose A C; Gaspar Danielle M; Magalhaes Hemerson I F; de Moraes Manoel O; Lobo Marina D P; Grangeiro Thalles B; Carvalho Tatiane S C; Diogo Emilay B T; da Silva Junior Eufranio N; Rodrigues Felipe A R; Cavalcanti Bruno C; Junior Helio V N^*

来源：PLos One, 2014, 9(5): e93698.

DOI：10.1371/journal.pone.0093698

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.

• 出版日期2014-5-9