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Antifungal activity, mode of action, docking prediction and anti-biofilm effects of (+)-β-pinene enantiomers against Candida spp.


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


Aims: The objective of this study was to investigate the effectiveness of (+)-β-pinene inhibition onCandida spp. growth,aiming at elucidation of the mechanism of action; to determinefungal cell enzymebinding activity (through molecular docking simulations) and its effects on biofilm reduction. Methodology:Candidastrains (n=26)from referencedand clinical origins, eithersusceptible 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 wereevaluatedby 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 simulationsindicatedbetter interactionwith delta-14-sterol reductase (−51 kcal/mol). (+)-β-pinene presents anti-biofilm activity againstmultiples species of Candida. Conclusion:(+)-β-pinene has antifungal activityand most likely acts throughinterference 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 molecules was also found to effectively reduceCandida biofilm adhesion.


Candidiasis, Products with Antimicrobial Action, Antifungal Agents, Drug Synergism, Molecular Docking Simulation


Federal University of Paraíba, Campus I, João Pessoa-PB, Piracicaba Dental School, University of Campinas, Piracicaba-SP, University of Florida College of Dentistry, Gainesville, FL, Federal University of Paraíba, Campus I, João Pessoa-PB, Federal University of Paraíba, Campus I, João Pessoa-PB, Federal University of Paraíba, Campus I, João Pessoa-PB, Federal University of Paraíba, Campus I, João Pessoa-PB

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