Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis
Abstract
1. Introduction
2. Results
2.1. Effect of NFT/MTF Combinations In Vitro and Ex Vivo
2.2. Effect of NFT/MTF Combination In Vivo
2.3. Inhibition of TR Activity
3. Discussion
4. Materials and Methods
4.1. Drugs
4.2. Experimental Animals and Ethical Statement
4.3. Parasites
4.4. Experimental Infections and Set Up of Primary Cultures
4.5. Axenic and Intramacrophagic Amastigotes Viability Assays
4.6. Cell Cytotoxicity
4.7. In Vivo Efficacy of Drug Combinations against L. donovani VL Mouse Model
4.8. Trypanothione Reductase (TR) Assay
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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CI Values at Following Effect Levels | ||||||||
---|---|---|---|---|---|---|---|---|
Drug/s | EC50 | Dm | m | r | 25% | 50% | 75% | 100% |
NFT | 0.02 ± 0.00 | 0.03 | 1.61 | 0.97 | *N/A | *N/A | *N/A | *N/A |
MTF | 0.63 ± 0.01 | 1.74 | 5.29 | 0.96 | *N/A | *N/A | *N/A | *N/A |
NFT/MTF 1/10 | N/A | 0.05 | 2.72 | 0.99 | 2.46 | 1.96 | 1.61 | 1.36 |
NFT/MTF 1/30 | N/A | 0.01 | 2.40 | 0.97 | 0.57 | 0.52 | 0.49 | 0.50 |
CI Values at Following Effect Levels | ||||||||
---|---|---|---|---|---|---|---|---|
Drug/s | EC50 | Dm | m | r | 25% | 50% | 75% | 100% |
NFT | 0.53 ± 0.05 | 0.09 | 0.94 | 0.92 | *N/A | *N/A | *N/A | *N/A |
MTF | 5.60 ± 0.38 | 2.19 | 1.20 | 0.95 | *N/A | *N/A | *N/A | *N/A |
NFT/MTF 1/10 | N/A | 0.36 | 3.34 | 0.94 | 4.93 | 2.82 | 1.65 | 1.00 |
NFT/MTF 1/30 | N/A | 0.002 | 0.23 | 0.84 | 0.002 | 0.06 | 2.43 | 98.06 |
DRI Values at Following Effect Levels | ||||
---|---|---|---|---|
Drug/s | 25% | 50% | 75% | 90% |
NFT MTF | NFT MTF | NFT MTF | NFT MTF | |
NFT/MTF 1/10 | 0.45 4.54 | 0.59 3.73 | 0.78 3.07 | 1.03 2.52 |
NFT/MTF 1/30 | 2.27 7.68 | 2.84 5.99 | 3.56 4.66 | 4.46 3.63 |
DRI Values at Following Effect Levels | ||||
---|---|---|---|---|
Drug/s | 25% | 50% | 75% | 90% |
NFT MTF | NFT MTF | NFT MTF | NFT MTF | |
NFT/MTF 1/10 | 0.49 0.35 | 0.72 0.70 | 1.05 1.42 | 1.54 2.87 |
NFT/MTF 1/30 | 1253.97 1301.74 | 36.52 29.53 | 1.06 0.67 | 0.03 0.01 |
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Melcon-Fernandez, E.; Galli, G.; García-Estrada, C.; Balaña-Fouce, R.; Reguera, R.M.; Pérez-Pertejo, Y. Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis. Int. J. Mol. Sci. 2023, 24, 1635. https://doi.org/10.3390/ijms24021635
Melcon-Fernandez E, Galli G, García-Estrada C, Balaña-Fouce R, Reguera RM, Pérez-Pertejo Y. Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis. International Journal of Molecular Sciences. 2023; 24(2):1635. https://doi.org/10.3390/ijms24021635
Chicago/Turabian StyleMelcon-Fernandez, Estela, Giulio Galli, Carlos García-Estrada, Rafael Balaña-Fouce, Rosa M. Reguera, and Yolanda Pérez-Pertejo. 2023. "Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis" International Journal of Molecular Sciences 24, no. 2: 1635. https://doi.org/10.3390/ijms24021635
APA StyleMelcon-Fernandez, E., Galli, G., García-Estrada, C., Balaña-Fouce, R., Reguera, R. M., & Pérez-Pertejo, Y. (2023). Miltefosine and Nifuratel Combination: A Promising Therapy for the Treatment of Leishmania donovani Visceral Leishmaniasis. International Journal of Molecular Sciences, 24(2), 1635. https://doi.org/10.3390/ijms24021635