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ANTIFUNGAL MECHANISM OF [RUIII(NH3)4CATECHOL]+ COMPLEX ON FLUCONAZOLE-RESISTANT CANDIDA TROPICALIS
Resistente ao fluconazol
Complexo de rutênio
catecol, agentes antifúngicos, candidíase
fluconazole-resistant
Ruthenium complex
catechol, antifungal agents, candidiasis
Author
Affilliation
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil
Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Uberlânida, MG, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas de Ribeirão Preto. Ribeirão Preto, SP, Brasil
Universidade Federal de Uberlândia. Faculdade de Ciências Integradas do Pontal. Uberlânida, MG, Brazil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Abstract
Candidiasis, a major opportunistic mycosis caused by Candida sp., may comprise life-threatening systemic infections. The incidence of non-albicans species is rising, particularly in South America and they are frequently drug resistant, causing unresponsive cases. Thus, novel antimycotic agents are required. Here we tested the antifungal activity of [RuIII(NH3)4catechol]+ complex (RuCat), approaching possible action mechanisms on fluconazole-resistant Candida tropicalis. RuCat significantly (P < 0.05) inhibited the growth and viability of C. tropicalis dose-dependently (IC50 20.3 μM). Cytotoxicity of RuCat upon murine splenocytes was lower (Selectivity Index = 16). Scanning electron microscopy analysis showed pseudohyphae formation, yeast aggregation and surface damage. RuCat-treated samples investigated by transmission electron microscopy showed melanin granule trafficking to cell surfaces and extracellular milieu. Surface-adherent membrane fragments and extracellular debris were also observed. RuCat treatment produced intense H2DCFDA labeling, indicating reactive oxygen species (ROS) production which caused increased lipoperoxidation. ROS are involved in the fungicidal effect as N-acetyl-L-cysteine completely restored cell viability. Calcofluor White chitin staining suggests that 70 or 140 μM RuCat treatment for 2 h affected cell-wall structure. PI labeling indicated necrotic cell death. The present data indicate that RuCat triggers ROS production, lipoperoxidation and cell surface damage, culminating in selective necrotic death of drug-resistant C. tropicalis.
Keywords in Portuguese
Candida tropicalisResistente ao fluconazol
Complexo de rutênio
catecol, agentes antifúngicos, candidíase
Keywords
Candida tropicalisfluconazole-resistant
Ruthenium complex
catechol, antifungal agents, candidiasis
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