Objective To investigate the antifungal activity of the fern species Lygodium venustum (L. venustum) and Pityrogramma calomelanos (P. calomelanos) against Candida albicans and Candida tropicalis strains. Methods The microdilution method was used to evaluate the antifungal activity, as well as the modulating effects of ethanolic extracts of these plants in combination with fluconazole. The minimum inhibitory concentration (MIC), minimum fungicide concentration and morphological changes were also determined. Results The extract obtained from L. venustum presented a MIC > 8 192 μg/mL, while the extract obtained from and P. calomelanos presented a MIC = 8 192 μg/mL, indicating that they present weak antifungal activity. However, combination of the extracts with Fluconazole potentiated the antifungal activity of this drug. At different experimental conditions, such as concentration of the extract and type of strain, the extracts inhibited hyphae and pseudohyphae formation, indicating that these fern species can affect the morphology of the fungi. Conclusions The extracts obtained from the fern species L. venustum and P. calomelanos dose not present significant antifungal activity. However, P. calomelanos potentiates the activity of fluconazole and both extracts inhibits the morphological changes in Candida species, indicating that they have potential pharmacological activity as modulators of fungal biology. Therefore, novel studies are required to characterize the interference of these extracts in the virulence and pathogenicity of Candida species as well as the potential of fern species to treat fungal infections.

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mechanisms in Staphylococcus aureus strains. Methods: Ferulic acid derivatives were obtained by esterification with methanol, ethanol, propanol, and butanol, and then characterized by hydrogen and carbon-13 nuclear magnetic resonance analysis. The minimum inhibitory concentrations (MIC) of ferulic acid and its esterified derivatives, ethidium bromide, and norfloxacin were obtained using the microdilution test, while the efflux pump inhibition test was conducted by examining reduction in the MICs of norfloxacin and ethidium bromide. Molecular docking was also carried out using the Schrodinger Suite 2015 molecular modeling software. A three-dimensional model of NorA efflux pump was generated using I-TASSER. The best scoring model was used as a receptor for ligand-receptor docking. Results: The methyl and butyl ester derivatives did not demonstrate significant antimicrobial activity. However, a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives. The docking study demonstrated favorable energy of interaction between ferulate derivatives and NorA, and amino acid residues TYR57, TYR58, and LEU255 were present commonly in stabilizing all complexes. The PCA analysis corroborated the docking hypothesis that the lipophilic character and hydrogen bond interactions were the most relevant characteristics involved with NorA inhibitors. The pharmacokinetic parameters of ferulic acid derivatives showed good ADMET properties, demonstrating that they can be easily absorbed and have no effect or inhibit the cytochrome P450 enzyme complex, revealing their potential as drug candidates. Conclusions: This study provides strong evidence that the molecular basis for this activity is potentially due to the NorA efflux pump.