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Antifungal activity of linalool against fluconazole-resistant clinical strains of vulvovaginal Candida albicans and its predictive mechanism of action
Medeiros, C.I.S.; Sousa, M.N.A. de; Filho, G.G.A.; Freitas, F.O.R.; Uchoa, D.P.L.; Nobre, M.S.C.; Bezerra, A.L.D.; Rolim, L.A.D.M.M.; Morais, A.M.B.; Nogueira, T.B.S.S.; Nogueira, R.B.S.S.; Filho, A.A.O.; Lima, E.O..
  • Medeiros, C.I.S.; Universidade Federal da Paraíba. Departamento de Ciências Farmacêuticas. João Pessoa. BR
  • Sousa, M.N.A. de; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Filho, G.G.A.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Freitas, F.O.R.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Uchoa, D.P.L.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Nobre, M.S.C.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Bezerra, A.L.D.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Rolim, L.A.D.M.M.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Morais, A.M.B.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Nogueira, T.B.S.S.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Nogueira, R.B.S.S.; Centro Universitário UniFIP. Curso de Medicina. Patos. BR
  • Filho, A.A.O.; Universidade Federal de Campina Grande. Unidade Acadêmica de Ciências Biológicas (UACB). Patos. BR
  • Lima, E.O.; Universidade Federal da Paraíba. Departamento de Ciências Farmacêuticas. João Pessoa. BR
Braz. j. med. biol. res ; 55: e11831, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1394125
ABSTRACT
Candida albicans is the most frequently isolated opportunistic pathogen in the female genital tract, with 92.3% of cases in Brazil associated with vulvovaginal candidiasis (VVC). Linalool is a monoterpene compound from plants of the genera Cinnamomum, Coriandrum, Lavandula, and Citrus that has demonstrated a fungicidal effect on strains of Candida spp., but its mechanism of action is still unknown. For this purpose, broth microdilution techniques were applied, as well as molecular docking in a predictive manner for this mechanism. The main results of this study indicated that the C. albicans strains analyzed were resistant to fluconazole and sensitive to linalool at a dose of 256 µg/mL. Furthermore, the increase in the minimum inhibitory concentration (MIC) of linalool in the presence of sorbitol and ergosterol indicated that this molecule possibly affects the cell wall and plasma membrane integrity of C. albicans. Molecular docking of linalool with proteins that are key in the biosynthesis and maintenance of the cell wall and the fungal plasma membrane integrity demonstrated the possibility of linalool interacting with three important enzymes 1,3-β-glucan synthase, lanosterol 14α-demethylase, and Δ 14-sterol reductase. In silico analysis showed that this monoterpene has theoretical but significant oral bioavailability, low toxic potential, and high similarity to pharmaceuticals. Therefore, the findings of this study indicated that linalool probably causes damage to the cell wall and plasma membrane of C. albicans, possibly by interaction with important enzymes involved in the biosynthesis of these fungal structures, in addition to presenting low in silico toxic potential.


Full text: Available Index: LILACS (Americas) Type of study: Prognostic study / Risk factors Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2022 Type: Article Affiliation country: Brazil Institution/Affiliation country: Centro Universitário UniFIP/BR / Universidade Federal da Paraíba/BR / Universidade Federal de Campina Grande/BR

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Full text: Available Index: LILACS (Americas) Type of study: Prognostic study / Risk factors Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 2022 Type: Article Affiliation country: Brazil Institution/Affiliation country: Centro Universitário UniFIP/BR / Universidade Federal da Paraíba/BR / Universidade Federal de Campina Grande/BR