Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p
Abstract
:1. Introduction
2. Materials and Methods
2.1. Strains and Culture Conditions
2.2. Chemicals
2.3. Antifungal Susceptibility Test
2.4. Disk Diffusion Assay
2.5. Checkerboard Assay
2.6. Rhodamine 6G Accumulation Assay
2.7. Preparation of Plasma Membranes
2.8. ATPase Activity
2.9. Hemolysis Assay
2.10. Statistical Analysis
3. Results
3.1. Antifungal Susceptibility Test
3.2. Disk Diffusion Assay
3.3. Checkerboard Assay
3.4. Rhodamine 6G Accumulation Assay
3.5. ATPase Activity
3.6. Hemolysis Assay
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Strain and Compound | Compound (µM) | Fluconazole (µg/mL) | ||||||
---|---|---|---|---|---|---|---|---|
MIC a | MIC c | FIC | MIC a | MIC c | FIC | FICI | Outcome | |
AD/124567 | ||||||||
DGB1 | 200 | 50 | 0.250 | 480 | 120 | 0.250 | 0.500 | S |
DGB2 DGB3 DGB4 DGB5 DGB6 DGB7 | 200 100 200 200 200 200 | 25 6.25 50 3.125 50 3.125 | 0.125 0.063 0.250 0.016 0.250 0.016 | 480 480 480 480 480 480 | 7.5 7.5 15 7.5 60 7.5 | 0.016 0.016 0.031 0.016 0.125 0.016 | 0.141 0.078 0.281 0.031 0.375 0.031 | S S S S S S |
95–142 | ||||||||
DGB1 | 200 | 25 | 0.125 | 62.5 | 31.25 | 0.500 | 0.625 | I |
DGB2 DGB3 DGB4 DGB5 DGB6 DGB7 | 200 200 200 200 200 200 | 200 6.25 200 200 200 200 | 1 0.031 1 1 1 1 | 62.5 62.5 62.5 62.5 62.5 62.5 | 62.5 15.63 62.5 62.5 62.5 62.5 | 1 0.250 1 1 1 1 | 2 0.281 2 2 2 2 | I S I I I I |
Compound | Rhodamine 6G Efflux (%) | IC50 (μM) | Molecular Weight | cLogP |
---|---|---|---|---|
DGB1 | 6.84 | 1.25 | 869 | 3.88 |
DGB2 | 1.31 | 0.49 | 899 | 3.81 |
DGB3 | 0.00 | 2.13 | 938 | 5.09 |
DGB4 | 23.35 | 2.19 | 887 | 3.98 |
DGB5 | 8.52 | 0.41 | 912 | 3.78 |
DGB6 | 4.66 | 0.53 | 914 | 2.96 |
DGB7 | 2.45 | 3.72 | 903 | 4.49 |
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de Moraes, D.C.; Tessis, A.C.; Rollin-Pinheiro, R.; Princival, J.L.; Villar, J.A.F.P.; Barbosa, L.A.; Barreto-Bergter, E.; Ferreira-Pereira, A. Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p. J. Fungi 2022, 8, 769. https://doi.org/10.3390/jof8080769
de Moraes DC, Tessis AC, Rollin-Pinheiro R, Princival JL, Villar JAFP, Barbosa LA, Barreto-Bergter E, Ferreira-Pereira A. Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p. Journal of Fungi. 2022; 8(8):769. https://doi.org/10.3390/jof8080769
Chicago/Turabian Stylede Moraes, Daniel Clemente, Ana Claudia Tessis, Rodrigo Rollin-Pinheiro, Jefferson Luiz Princival, José Augusto Ferreira Perez Villar, Leandro Augusto Barbosa, Eliana Barreto-Bergter, and Antônio Ferreira-Pereira. 2022. "Digoxin Derivatives Sensitize a Saccharomyces cerevisiae Mutant Strain to Fluconazole by Inhibiting Pdr5p" Journal of Fungi 8, no. 8: 769. https://doi.org/10.3390/jof8080769