Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde

Graduate Program in Natural and Synthetic Bioactive Products (PgPNSB), Department of Clinic and Social Dentistry, Center for Health Sciences, Federal University of Paraiba, João Pessoa-PB 58051-900, Brazil

Graduate Program in Natural and Synthetic Bioactive Products (PgPNSB), Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil

Experimental Pharmacology and Cell Culture Laboratory, Center for Health Sciences, Federal University of Paraiba, João Pessoa-PB 58051-900, Brazil

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Department of Bioscience, Piracicaba Dental School, University of Campinas, Campinas-SP 13414-903, Brazil

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Department of Physiology and Pathology, Center for Health Sciences, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil

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Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil

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Graduate Program in Natural and Synthetic Bioactive Products (PgPNSB), Department of Chemistry, Center for Health Sciences, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil

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Graduate Program in Natural and Synthetic Bioactive Products (PgPNSB), Cheminformatics Laboratory, Center for Health Sciences, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil

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Biological Sciences Graduate Program (PPGCB), Institute of Biomedical Sciences (ICB), Federal University of Alfenas (UNIFAL-MG), Alfenas 37130-000, Brazil

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Department of Clinic and Social Dentistry, Center for Health Sciences, Federal University of Paraiba, João Pessoa-PB 58051-900, Brazil

Author to whom correspondence should be addressed.

Academic Editors: Diego Muñoz-Torrero, Rossella Grande and Simone Carradori

Molecules 2020, 25(24), 5969; https://doi.org/10.3390/molecules25245969

Received: 4 November 2020 / Revised: 19 November 2020 / Accepted: 20 November 2020 / Published: 16 December 2020

(This article belongs to the Special Issue Novel Biologically Active Molecules, Biomaterials and Nanoparticles for the Microbial Biofilm Control in Human Medicine)

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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. View Full-Text

Keywords: candidiasis; antimicrobial products; antifungal; molecular coupling simulation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

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MDPI and ACS Style

da Nóbrega Alves, D.; Monteiro, A.F.M.; Andrade, P.N.; Lazarini, J.G.; Abílio, G.M.F.; Guerra, F.Q.S.; Scotti, M.T.; Scotti, L.; Rosalen, P.L.; Castro, R.D.d. Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde. Molecules 2020, 25, 5969. https://doi.org/10.3390/molecules25245969

AMA Style

da Nóbrega Alves D, Monteiro AFM, Andrade PN, Lazarini JG, Abílio GMF, Guerra FQS, Scotti MT, Scotti L, Rosalen PL, Castro RDd. Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde. Molecules. 2020; 25(24):5969. https://doi.org/10.3390/molecules25245969

Chicago/Turabian Style

da Nóbrega Alves, Danielle, Alex F.M. Monteiro, Patrícia N. Andrade, Josy G. Lazarini, Gisely M.F. Abílio, Felipe Q.S. Guerra, Marcus T. Scotti, Luciana Scotti, Pedro L. Rosalen, and Ricardo D.d. Castro. 2020. "Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde" Molecules 25, no. 24: 5969. https://doi.org/10.3390/molecules25245969

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Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde

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