In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri
Abstract
:1. Introduction
2. Results and Discussion
2.1. In Vitro Effect of Lonafarnib against Different Clinical Strains of N. fowleri
2.2. Effect of Combination of Lonafarnib and Pitavastatin on N. fowleri
2.3. Microscopic Evaluation to Determine the Effect of Combination of Lonafarnib and Pitavastatin at Different Time Points
3. Materials and Methods
3.1. Maintenance of N. fowleri Culture
3.2. In Vitro Effect of Lonafarnib against Different Clinical Strains of N. fowleri
3.3. Effect of Combination of Lonafarnib and Pitavastatin on N. fowleri
3.4. Microscopic Evaluation to Determine the Effect of Combination of Lonafarnib and Pitavastatin at Different Time Points
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Strain | EC50 (µM) Mean ± SE |
---|---|---|
Lonafarnib | KUL | 1.5 ± 0.1 |
CDC:V1005 | 2.5 ± 0.04 | |
US Davis (Genotype I) | 5 ± 0.09 | |
US CAMP (Genotype II) | 3.5 ± 0.05 | |
US TY (Genotype III) | 9.2 ± 0.05 |
Lonafarnib:Pitavastatin Ratio | % Growth Inhibition of N. fowleri KUL Trophozoites | Combination Index (CI) | Dose Reduction Index (DRI) | Dose Required to Achieve 95% Inhibition (µM) | ||
---|---|---|---|---|---|---|
Lonafarnib | Pitavastatin | Lonafarnib | Pitavastatin | |||
1:1 | 95 | 0.36 | 5.1 | 6.1 | 3.1 | 3.1 |
1:2 | 95 | 0.29 | 9.2 | 5.5 | 1.7 | 3.4 |
1:4 | 95 | 0.29 | 14.9 | 4.5 | 1 | 4.2 |
1:8 | 95 | 0.38 | 19.9 | 3 | 0.8 | 6.2 |
1:16 | 95 | 0.46 | 31.4 | 2.4 | 0.5 | 7.9 |
2:1 | 95 | 0.38 | 3.8 | 9 | 4.1 | 2.1 |
4:1 | 95 | 0.53 | 2.3 | 11.1 | 6.8 | 1.7 |
8:1 | 95 | 0.59 | 1.9 | 18.1 | 8.3 | 1 |
16:1 | 95 | 0.73 | 1.4 | 27.6 | 10.8 | 0.7 |
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Hahn, H.J.; Debnath, A. In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri. Pathogens 2020, 9, 689. https://doi.org/10.3390/pathogens9090689
Hahn HJ, Debnath A. In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri. Pathogens. 2020; 9(9):689. https://doi.org/10.3390/pathogens9090689
Chicago/Turabian StyleHahn, Hye Jee, and Anjan Debnath. 2020. "In Vitro Evaluation of Farnesyltransferase Inhibitor and its Effect in Combination with 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor against Naegleria fowleri" Pathogens 9, no. 9: 689. https://doi.org/10.3390/pathogens9090689