Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action

Morais, Mayara Castro de; Pérez-Castillo, Yunierkis; Silva, Valdenizia Rodrigues; Santos, Luciano de S.; Soares, Milena Botelho Pereira; Bezerra, Daniel P.; Sousa, Damião Pergentino de

doi:10.1155/2021/3598000

Cited by 9 publications

(14 citation statements)

References 82 publications

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“…One may analyze whether a substance is fungicidal or fungistatic by calculating its MFC to MIC ratio [ 76 ]. Therefore, MFC/MIC ratios were calculated to determine whether the substances presented fungistatic (MFC/MIC > 4) or fungicidal (MFC/MIC ≤ 4) activity.…”

Section: Resultsmentioning

confidence: 99%

“…Sterols make up part of the constitution of all fungal cells. Ergosterol is a principal sterol and modulates membrane fluidity, cell growth, and proliferation [ 76 ]. In this study, tests to detect the biological targets of compounds 4 and 6 were performed by adding ergosterol to the medium.…”

Section: Resultsmentioning

confidence: 99%

“…An increase in the MIC of the compounds was observed, indicating that the fungus likely acts by inhibiting ergosterol synthesis or directly binding to ergosterol. Azoles and polyenes are well-known classes of antifungal drugs that act on ergosterol to treat fungal infections [ 76 ] ( Table 3 and Table 4 ).…”

Section: Resultsmentioning

confidence: 99%

“…When studying cell wall architecture, protoplasts stabilized with osmo-protectants are important biochemical tools [ 76 ]. Osmotic stability is used with C. albicans and other fungi to study antibiotic mechanisms of action [ 76 , 77 , 78 ].…”

Section: Resultsmentioning

confidence: 99%

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Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

et al. 2023

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The severity of infectious diseases associated with the resistance of microorganisms to drugs highlights the importance of investigating bioactive compounds with antimicrobial potential. Therefore, nineteen synthetic cinnamides and cinnamates having a cinnamoyl nucleus were prepared and submitted for the evaluation of antimicrobial activity against pathogenic fungi and bacteria in this study. To determine the minimum inhibitory concentration (MIC) of the compounds, possible mechanisms of antifungal action, and synergistic effects, microdilution testing in broth was used. The structures of the synthesized products were characterized with FTIR spectroscopy, 1 H-NMR, 13 C-NMR, and HRMS. Derivative 6 presented the best antifungal profile, suggesting that the presence of the butyl substituent potentiates its biological response (MIC = 626.62 μM), followed by compound 4 (672.83 μM) and compound 3 (726.36 μM). All three compounds were fungicidal, with MFC/MIC ≤ 4. For mechanism of action, compounds 4 and 6 directly interacted with the ergosterol present in the fungal plasmatic membrane and with the cell wall. Compound 18 presented the best antibacterial profile (MIC = 458.15 μM), followed by compound 9 (550.96 μM) and compound 6 (626.62 μM), which suggested that the presence of an isopropyl group is important for antibacterial activity. The compounds were bactericidal, with MBC/MIC ≤ 4. Association tests were performed using the Checkerboard method to evaluate potential synergistic effects with nystatin (fungi) and amoxicillin (bacteria). Derivatives 6 and 18 presented additive effects. Molecular docking simulations suggested that the most likely targets of compound 6 in C. albicans were caHOS2 and caRPD3, while the most likely target of compound 18 in S. aureus was saFABH. Our results suggest that these compounds could be used as prototypes to obtain new antimicrobial drugs.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

et al. 2023

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“…Amber 20 [83] was used for molecular dynamics (MD) simulations as described in our previous publication [84]. The same preparation, energy minimization, heating, equilibration, and production runs protocol were applied to all complexes.…”

Section: Molecular Dynamics Simulations and Estimation Of Free Energi...mentioning

confidence: 99%

Synthesis of Coumarin and Homoisoflavonoid Derivatives and Analogs: The Search for New Antifungal Agents

et al. 2022

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A set of twenty-four synthetic derivatives, with coumarin and homoisoflavonoid cores and structural analogs, were submitted for evaluation of antifungal activity against various species of Candida. The broth microdilution test was used to determine the Minimum Inhibitory Concentration (MIC) of the compounds and to verify the possible antifungal action mechanisms. The synthetic derivatives were obtained using various reaction methods, and six new compounds were obtained. The structures of the synthesized products were characterized by FTIR spectroscopy: 1H-NMR, 13C-NMR, and HRMS. The coumarin derivative 8 presented the best antifungal profile, suggesting that the pentyloxy substituent at the C-7 position of coumarin ring could potentiate the bioactivity. Compound 8 was then evaluated against the biofilm of C. tropicalis ATCC 13803, which showed a statistically significant reduction in biofilm at concentrations of 0.268 µmol/mL and 0.067 µmol/mL, when compared to the growth control group. For a better understanding of their antifungal activity, compounds 8 and 21 were submitted to a study of the mode of action on the fungal cell wall and plasma membrane. It was observed that neither compound interacted directly with ergosterol present in the fungal plasma membrane or with the fungal cell wall. This suggests that their bioactivity was due to interaction involving other pharmacological targets. Compound 8 was also subjected to a molecular modeling study, which showed that its antifungal action mechanism occurred mainly through interference in the redox balance of the fungal cell, and by compromising the plasma membrane; not by direct interaction, but by interference in ergosterol synthesis. Another important finding was the antifungal capacity of homoisoflavonoids 23 and 24. Derivative 23 presented slightly higher antifungal activity, possibly due to the presence of the methoxyl substituent in the meta position in ring B.

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Mechanistic insight into pharmacological effects of secondary metabolites from Bidens pilosa

Mwesigwa,

Ssempijja,

Kyada

2024

Phytochem Rev

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Cytotoxic and Antifungal Amides Derived from Ferulic Acid: Molecular Docking and Mechanism of Action

Cited by 9 publications

References 82 publications

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

Synthetic Cinnamides and Cinnamates: Antimicrobial Activity, Mechanism of Action, and In Silico Study

Synthesis of Coumarin and Homoisoflavonoid Derivatives and Analogs: The Search for New Antifungal Agents

Mechanistic insight into pharmacological effects of secondary metabolites from Bidens pilosa

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