Antifungal activity of linalool against fluconazole-resistant clinical strains of vulvovaginal Candida albicans and its predictive mechanism of action

被引：0

作者：

Medeiros, C. I. S. ^{[1
,2
]}

de Sousa, M. N. A. ^{[2
]}

Filho, G. G. A. ^{[2
]}

Freitas, F. O. R. ^{[2
]}

Uchoa, D. P. L. ^{[2
]}

Nobre, M. S. C. ^{[2
]}

Bezerra, A. L. D. ^{[2
]}

Rolim, L. A. D. M. M. ^{[2
]}

Morais, A. M. B. ^{[2
]}

Nogueira, T. B. S. S. ^{[2
]}

Nogueira, R. B. S. S. ^{[2
]}

Filho, A. A. O. ^{[3
]}

Lima, E. O. ^{[1
]}

机构：

[1] Univ Fed Paraiba, Dept Ciencias Farmaceut, Joao Pessoa, Paraiba, Brazil

[2] Ctr Univ UniFIP, Curso Med, Patos de Minas, PB, Brazil

[3] Univ Fed Campina Grande, Unidade Acad Ciencias Biol UACB, Patos de Minas, PB, Brazil

来源：

BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH | 2022年 / 55卷 / 01期

关键词：

Linalool; Antifungal resistance; Fluconazole; Vulvovaginal candidiasis; Mechanism of action; ANTIMICROBIAL ACTIVITY; ASSAY;

D O I：

10.1590/1414-431X2022e11831

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 mu g/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-beta-glucan synthase, lanosterol 14 alpha-demethylase, and Delta 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.

引用

页数：11