Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde
Danielle da Nóbrega Alves, Alex Monteiro, Patrícia Néris Andrade, Josy Goldoni Lazarini, Gisely Maria Freire Abílio, Felipe Queiroga Sarmento Guerra, Marcus Tullius Scotti, Luciana Scotti, Pedro Luiz Rosalen, Ricardo Dias de Castro
Abstract
Objective: This study evaluated the antifungal activity of cinnamaldehyde on Candida spp. In vitro and in situ assays were carried out to test cinnamaldehyde for its anti-Candida effects, antibiofilm activity, effects on fungal micromorphology, antioxidant activity, and toxicity on keratinocytes and human erythrocytes. Statistical analysis was performed considering α = 5%. Results: The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of cinnamaldehyde ranged from 18.91 μM to 37.83 μM. MIC values did not change in the presence of 0.8 M sorbitol, whereas an 8-fold increase was observed in the presence of ergosterol, suggesting that cinnamaldehyde may act on the cell membrane, which was subsequently confirmed by docking analysis. The action of cinnamaldehyde likely includes binding to enzymes involved in the formation of the cytoplasmic membrane in yeast cells. Cinnamaldehyde-treated microcultures showed impaired cellular development, with an expression of rare pseudo-hyphae and absence of chlamydoconidia. Cinnamaldehyde reduced biofilm adherence by 64.52% to 33.75% (p < 0.0001) at low concentrations (378.3–151.3 µM). Cinnamaldehyde did not show antioxidant properties. Conclusions: Cinnamaldehyde showed fungicidal activity through a mechanism of action likely related to ergosterol complexation; it was non-cytotoxic to keratinocytes and human erythrocytes and showed no antioxidant activity.