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

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

Volume: 18 Issue: 29

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

Affiliation:

• Federal University of Paraiba, Campus I, Joao Pessoa, PB,Brazil

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

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.

Cite this article as:

de Macêdo Andrade Cláudia Ana , Rosalen Luiz Pedro , Freires Almeida Irlan , Scotti Luciana *, Scotti Tulius Marcus , Aquino Garcia Sabrina and de Castro Dias Ricardo , Antifungal Activity, Mode of Action, Docking Prediction and Anti-biofilm Effects of (+)-β-pinene Enantiomers against Candida spp., Current Topics in Medicinal Chemistry 2018; 18 (29) . https://dx.doi.org/10.2174/1568026618666181115103104