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Antifungal Activity Directed Toward the Cell Wall by 2-Cyclohexylidenhydrazo- 4-Phenyl-Thiazole Against Candida albicans

[ Vol. 19 , Issue. 4 ]

Author(s):

Nívea P. de Sá*, Ana P. Pôssa*, Pilar Perez, Jaqueline M.S. Ferreira, Nayara C. Fonseca, Cleudiomar I. Lino, Lana B. Cruz, Renata B. de Oliveira, Carlos A. Rosa, Beatriz M. Borelli, Eleftherios Mylonakis, Beth B. Fuchs and Susana Johann   Pages 428 - 438 ( 11 )

Abstract:


Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds.

Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans.

Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans.

Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase.

Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.

Keywords:

Anticandidal activity, β-glucan, Candida albicans, 2-cyclohexylidenhydrazo-4-phenyl-thiazole, Synthetic compounds, Virulence.

Affiliation:

Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Antonio Carlos, 6627, Pampulha – CEP 31270-901, Belo Horizonte – MG, Laboratorio de Microbiologia, Campus Centro- Oeste Dona Lindu, Universidade Federal de Sao Joao del-Rei, Divinópolis, Minas Gerais, Instituto de Biologia Fundamental y Genomica CSIC, Universidad de Salamanca, Salamanca, Laboratorio de Microbiologia, Campus Centro- Oeste Dona Lindu, Universidade Federal de Sao Joao del-Rei, Divinópolis, Minas Gerais, Departamento de Produtos Farmaceuticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais, Belo Horizonte – MG, Departamento de Produtos Farmaceuticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais, Belo Horizonte – MG, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Antonio Carlos, 6627, Pampulha – CEP 31270-901, Belo Horizonte – MG, Departamento de Produtos Farmaceuticos, Faculdade de Farmacia, Universidade Federal de Minas Gerais, Belo Horizonte – MG, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Antonio Carlos, 6627, Pampulha – CEP 31270-901, Belo Horizonte – MG, Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Antonio Carlos, 6627, Pampulha – CEP 31270-901, Belo Horizonte – MG, Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, and Brown University, Providence, RI, Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, and Brown University, Providence, RI, Instituto de Biologia Fundamental y Genomica CSIC, Universidad de Salamanca, Salamanca

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