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.

The genus Acinetobacter has gained importance in recent years due to involvement in serious infections and antimicrobial resistance. Many plants have been evaluated not only for direct antimicrobial activity, but also as resistance modifying agents. The Essential oil of Citrus limon (EOCL) addition at 156.25 µgmL⁻¹ (MIC/8) sub-inhibitory concentration in the growth medium led to MIC decrease for amikacin, imipenem and meropenem. The Essential oil of Cinnamomum zeylanicum (EOCZ) addition at 78.125 µg mL⁻¹ (MIC/8) sub-inhibitory concentrations in the growth medium caused drastic MIC reduction of amikacin. Results of combining antibiotics and essential oils had shown us a synergistic effect with both essential oils/amikacin combinations. An additive effect was observed with the combinations of both essential oils and gentamicin. The results of this study suggest that essential oil of C. limon and C. zeylanicum may suppress the growth of Acinetobacter species and could be a source of metabolites with antibacterial modifying activity.

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO₂ and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r² of 0.86 and q²_cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

Candida albicans is associated with serious infections in immunocompromised patients. Terpenes are natural-product derivatives, widely studied as antifungal alternatives. In a previous study reported by our group, the antifungal activity of α-pinene against C. albicans was verified; α-pinene presented an MIC between 128–512 µg/mL. In this study, we evaluate time-kill, a mechanism of action using in silico and in vitro tests, anti-biofilm activity against the Candida albicans, and toxicity against human cells (HaCaT). Results from the molecular-docking simulation demonstrated that thymidylate synthase (−52 kcal mol⁻¹), and δ-14-sterol reductase (−44 kcal mol⁻¹) presented the best interactions. Our in vitro results suggest that α-pinene’s antifungal activity involves binding to ergosterol in the cellular membrane. In the time-kill assay, the antifungal activity was not time-dependent, and also inhibited biofilm formation, while rupturing up to 88% of existing biofilm. It was non-cytotoxic to human keratinocytes. Our study supports α-pinene as a candidate to treat fungal infections caused by C. albicans.

Aspergillusspp. produce a wide variety of diseases. For the treatment of such infections, the azoles and Amphotericin B are used in various formulations. The treatment of fungal diseases is often ineffective, because of increases in azole resistance and their several associated adverse effects. To overcome these problems, natural products and their derivatives are interesting alternatives. The aim of this study was to examine the effects of coumarin derivative, 7-hydroxy-6-nitro-2H-1-benzopyran-2-one (Cou-NO₂), both alone and with antifungal drugs. Its mode of action againstAspergillusspp. Cou-NO₂was tested to evaluate its effects on mycelia growth and germination of fungal conidia ofAspergillusspp. We also investigated possible Cou-NO₂action on cell walls (0.8 M sorbitol) and on Cou-NO₂to ergosterol binding in the cell membrane. The study shows that Cou-NO₂is capable of inhibiting both the mycelia growth and germination of conidia for the species tested, and that its action affects the structure of the fungal cell wall. At subinhibitory concentration, Cou-NO₂enhanced thein vitroeffects of azoles. Moreover, in combination with azoles (voriconazole and itraconazole) Cou-NO₂displays an additive effect. Thus, our study supports the use of coumarin derivative 7-hydroxy-6-nitro-2H-1-benzopyran-2-one as an antifungal agent againstAspergillusspecies.

A limited number of antifungals and the emergence of resistant strains have hindered the treatment of candidiasis, making the search for new antifungals urgent. Citral is a monoterpene with known pharmacological properties, including antimicrobial action. Aims: Thus the objective of this study was to investigate the possible mechanism of citral’s action against Candida tropicalis isolated from human blood, and the effect of its association with antifungals. Methodology: The minimum inhibitory concentration (MIC), the minimum fungicidal concentration (MFC), the effect of citral on the cell wall (sorbitol assay), and membrane ergosterol binding were evaluated using broth microdilution technique. We also evaluated interference in ergosterol biosynthesis, and the citral-antifungal association effect (checkerboard method). Results: The MIC₉₀ and MFC₉₀ of citral were respectively 512 and 1024 μg / mL. The MIC of citral did not increase when sorbitol or ergosterol was added to the medium, suggesting that citral does not act on the cell wall or by membrane ergosterol binding. However, citral inhibited ergosterol biosynthesis, and the citral-fluconazole combination showed synergistic effects for the ATCC strain. Conclusion: This study contributes to understanding the antifungal mechanism of citral’s action, and to the development of new therapies for candidiasis treatment.