Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes
Abstract
:1. Introduction
2. Results
2.1. In Vitro Efficacy of Nitroimidazole Compounds on L. infantum-iRFP Amastigotes
2.2. In Vitro Safety of Nitroimidazole Compounds on HepG2 and RAW 264.7 Mammalian Cells
2.3. Induction of ROS Production in L. infantum by Fexinidazole and Pretomanid
2.4. In Vitro Inhibitory Effect of Fexinidazole and Pretomanid on L. infantum TryR
3. Discussion
4. Materials and Methods
4.1. Experimental Animals and Ethical Statement
4.2. Nitroimidazole Compounds
4.3. Parasites and Mammalian Cell Lines
4.4. Assessment of In Vitro Cytotoxicity
4.5. Analysis of ROS Production by Axenic Amastigotes
4.6. Trypanothione Reductase Enzymatic Assay
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Tested Compound | Axenic Amastigotes | HepG2 Cells | RAW 264.7 Cells | SI1 | SI2 | |||
---|---|---|---|---|---|---|---|---|
EC50 Values (μM) | p | CC50 Values (μM) | p | CC50 Values (μM) | p | |||
Fexinidazole | 0.04 ± 0.00 | *** | >200.00 | N/A | >200.00 | N/A | >5000.00 | >5000.00 |
Pretomanid | 0.28 ± 0.02 | *** | >200.00 | N/A | >200.00 | N/A | >714.29 | >714.29 |
Amp B | 0.27 ± 0.02 | *** | 69.75 ± 13.69 | *** | 6.70 ± 0.67 | *** | 258.33 | 24.82 |
Tested Compound | Intramacrophage Amastigotes | HepG2 Cells | RAW 264.7 Cells | SI1 | SI2 | |||
---|---|---|---|---|---|---|---|---|
EC50 Values (μM) | p | CC50 Values (μM) | p | CC50 Values (μM) | p | |||
Fexinidazole | 1.32 ± 0.06 | *** | >200.00 | N/A | >200.00 | N/A | >151.52 | >151.52 |
Pretomanid | 0.66 ± 0.08 | *** | >200.00 | N/A | >200.00 | N/A | >303.03 | >303.03 |
Amp B | 0.32 ± 0.02 | *** | 69.75 ± 13.69 | *** | 6.70 ± 0.67 | *** | 217.97 | 20.94 |
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Andrés-Rodríguez, J.; González-Montero, M.-C.; García-Fernández, N.; Calvo-Álvarez, E.; Pérez-Pertejo, M.-Y.; Reguera-Torres, R.-M.; Balaña-Fouce, R.; García-Estrada, C. Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes. Molecules 2024, 29, 4041. https://doi.org/10.3390/molecules29174041
Andrés-Rodríguez J, González-Montero M-C, García-Fernández N, Calvo-Álvarez E, Pérez-Pertejo M-Y, Reguera-Torres R-M, Balaña-Fouce R, García-Estrada C. Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes. Molecules. 2024; 29(17):4041. https://doi.org/10.3390/molecules29174041
Chicago/Turabian StyleAndrés-Rodríguez, Julia, María-Cristina González-Montero, Nerea García-Fernández, Estefanía Calvo-Álvarez, María-Yolanda Pérez-Pertejo, Rosa-María Reguera-Torres, Rafael Balaña-Fouce, and Carlos García-Estrada. 2024. "Free Radical Production Induced by Nitroimidazole Compounds Lead to Cell Death in Leishmania infantum Amastigotes" Molecules 29, no. 17: 4041. https://doi.org/10.3390/molecules29174041