title: Terpinen-4-ol, tyrosol, and β-lapachone as potential antifungals against dimorphic fungi.
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.
authors: 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.
authors: Raimunda Sâmia Nogueira
authors: RS
authors: Brilhante
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Érica Pacheco
authors: ÉP
authors: Caetano
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Rita Amanda Chaves de
authors: RA
authors: Lima
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Francisca Jakelyne de Farias
authors: FJ
authors: Marques
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Débora de Souza Collares Maia
authors: DS
authors: Castelo-Branco
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Charlline Vládia Silva de
authors: CV
authors: Melo
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Glaucia Morgana de Melo
authors: GM
authors: Guedes
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: Jonathas Sales de
authors: JS
authors: Oliveira
authors: Federal University of São Paulo, Department of Microbiology, Immunology and Parasitology, Cellular Biology Division, São Paulo, SP, Brazil.
authors: Zoilo Pires de
authors: ZP
authors: Camargo
authors: Federal University of Ceará, Fortaleza, Postgraduate Program in Medical Microbiology, Specialized Medical Mycology Center, CE, Brazil.
authors: José Luciano Bezerra
authors: JL
authors: Moreira
authors: Federal University of Ceará, Fortaleza, Department of Statistics and Applied Mathematics, Fortaleza, CE, Brazil.
authors: André Jalles
authors: AJ
authors: Monteiro
authors: Christus College - Unichristus, Fortaleza, School of Medicine, Forteleza, CE, Brazil.
authors: Tereza de Jesus Pinheiro Gomes
authors: TJ
authors: Bandeira
authors: 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.
authors: Rossana de Aguiar
authors: RA
authors: Cordeiro
authors: 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.
authors: Marcos Fábio Gadelha
authors: MF
authors: Rocha
authors: 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.
authors: José Júlio Costa
authors: JJ
authors: Sidrim
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004875:Ergosterol / Q000378:metabolism; D005658:Fungi / Q000145:classification / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000494:pharmacology*; D009997:Osmotic Pressure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D009285:Naphthoquinones; D013729:Terpenes; C011867:4-hydroxyphenylethanol; C034019:terpinenol-4; C014638:beta-lapachone; D010626:Phenylethyl Alcohol; D004875:Ergosterol
keywords: Dimorphic fungi; Inhibitory effect; Terpinen-4-ol; Tyrosol; β-Lapachone