Antifungal Activity, Mode of Action, Docking Prediction and Anti-biofilm Effects of (+)-β-pinene Enantiomers against Candida spp.

Author(s): Ana Cláudia de Macêdo Andrade, Pedro Luiz Rosalen, Irlan Almeida Freires, Luciana Scotti*, Marcus Tulius Scotti, Sabrina Garcia Aquino, Ricardo Dias de Castro.

Journal Name: Current Topics in Medicinal Chemistry

Volume 18 , Issue 29 , 2018

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Abstract:

Aims: The objective of this study was to investigate the effectiveness of (+)-β-pinene inhibition on Candida spp. growth, aiming at elucidation of the mechanism of action; to determine fungal cell enzyme binding activity (through molecular docking simulations) and its effects on biofilm reduction.

Methods: Candida strains (n=25) from referenced and clinical origins, either susceptible or resistant to standard clinical antifungals, were tested for determination of Minimum Inhibitory Concentration (MIC); Minimum Fungicidal Concentration (MFC); and microbial death curves upon treatment with (+)-β-pinene; the effects of (+)-β-pinene on the cell wall (sorbitol assay), membrane ergosterol binding, and effects on biofilm were evaluated by microdilution techniques. We also evaluated the interactions between (+)-β-pinene and cell wall and membrane enzymes of interest.

Results: The MIC values of (+)-β-pinene ranged from <56.25 to 1800 µmol/L. The MIC of (+)-β-pinene did not increase when ergosterol was added to the medium, however it did increase in the presence of sorbitol, leading to a doubled MIC for C. tropicalis and C. krusei. The results of the molecular docking simulations indicated better interaction with delta-14-sterol reductase (−51 kcal/mol). (+)-β-pinene presents anti-biofilm activity against multiples species of Candida.

Conclusion: (+)-β-pinene has antifungal activity and most likely acts through interference with the cell wall; through molecular interaction with Delta-14-sterol reductase and, to a lesser extent, with the 1,3-β- glucan synthase. This molecule was also found to effectively reduce Candida biofilm adhesion.

Keywords: Candidiasis, Products with antimicrobial action, Antifungal agents, Drug synergism, Molecular docking simulation.

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Article Details

VOLUME: 18
ISSUE: 29
Year: 2018
Page: [2481 - 2490]
Pages: 10
DOI: 10.2174/1568026618666181115103104
Price: $58

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