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Braz J Microbiol. 2016 Oct - Dec;47(4):917-924. doi: 10.1016/j.bjm.2016.07.015. Epub 2016 Jul 26.

Terpinen-4-ol, tyrosol, and β-lapachone as potential antifungals against dimorphic fungi.

Author information

1
Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil; Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Sciences, CE, Brazil. Electronic address: brilhante@ufc.br.
2
Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
3
Federal University of São Paulo, Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, São Paulo, SP, Brazil.
4
Federal University of Ceará, Fortaleza, Department of Statistics and Applied Mathematics, Fortaleza, CE, Brazil.
5
Christus College - Unichristus, Fortaleza, School of Medicine, Forteleza, CE, Brazil.
6
Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil; Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Sciences, CE, Brazil.
7
Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil; State University of Ceará, Fortaleza, Postgraduate Program in Veterinary Sciences, Forteleza, CE, Brazil.

Abstract

This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-lapachone against strains of Coccidioides posadasii in filamentous phase (n=22) and Histoplasma capsulatum in both filamentous (n=40) and yeast phases (n=13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720μg/mL, 20-2860μg/mL, and 40-1420μg/mL, respectively for terpinen-4-ol; 250-4000μg/mL, 30-2000μg/mL, and 10-1000μg/mL, respectively, for tyrosol; and 0.48-7.8μg/mL, 0.25-16μg/mL, and 0.125-4μg/mL, respectively for β-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

KEYWORDS:

Dimorphic fungi; Inhibitory effect; Terpinen-4-ol; Tyrosol; β-Lapachone

PMID:
27520529
PMCID:
PMC5052391
DOI:
10.1016/j.bjm.2016.07.015
[Indexed for MEDLINE]
Free PMC Article

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