Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria
Abstract
:1. Introduction
2. Materials and Methods
2.1. Hydrazones and Anti-TB Drugs
Analytical
2.2. Bacterial Culture
2.3. Minimal Inhibitory Concentration (MIC90) Evaluation against Replicating M. tuberculosis and M. smegmatis
2.4. Minimal Inhibitory Concentration Evaluation against Non-Replicating M. tuberculosis
2.5. Cytotoxicity against Eukaryotic Cells
2.6. Determination of the Selectivity Index
2.7. Intramacrophagic Activity
2.8. Time-Kill Curve
2.9. Evaluation of Activity Spectrum
3. Results
3.1. Minimum Inhibitory Concentration (MIC90) Values against M. tuberculosis in an Active and Non-Replicating Metabolic State
3.2. Cytotoxicity Index (IC50) and Selectivity Index (SI) Results against Macrophage Cells and Lung Fibroblasts at 24, 48, and 72 h
3.3. Intramacrophagic Activity
3.4. Time-Kill Curve
3.5. Spectrum Activity
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
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Compounds | MIC90 1 Replicating | MIC90 Non-Replicating | ||
---|---|---|---|---|
μM | μg/mL | μM | μg/mL | |
Hydrazone 14 | 1.23 ± 0.53 | 0.35 ± 0.15 | 6.31 ± 5.72 | 1.77 ± 1.61 |
Hydrazone 16 | 6.01 ± 0.22 | 1.82 ± 0.68 | 7.76 ± 5.70 | 2.35 ± 1.73 |
Rifampicin | 0.05 ± 0.001 | 0.04 ± 0.01 | <0.36 | <0.3 |
Isoniazid | 0.44 ± 0.29 | 0.06 ± 0.04 | >328.13 | >45.0 |
IC50 (μg/mL) | IS | ||||||
---|---|---|---|---|---|---|---|
Cells | Time | H14 | H16 | INH | H14 | H16 | INH |
J774A.1 | 24 h | >100 | >100 | >100 | >289.02 | >54.85 | >1666.66 |
48 h | 83.34 ± 28.85 | 95.60 ± 7.61 | >100 | 240.88 | 52.44 | >1666.66 | |
72 h | 81.81 ± 31.50 | 72.29 ± 47.99 | >100 | 236.46 | 39.65 | >1666.66 | |
MRC-5 | 24 h | >100 | >100 | >100 | >289.02 | >54.85 | >1666.66 |
48 h | >100 | 96.23 ± 6.53 | >100 | >289.02 | 52.79 | >1666.66 | |
72 h | >100 | 67.43 ± 28.66 * | >100 | >289.02 | 36.99 | >1666.66 |
Molecules | S. typhimurium | P. aeruginosa | S. aureus | E. coli | M. smegmatis |
---|---|---|---|---|---|
14 | >100 | >100 | >100 | >100 | >25.0 |
16 | >100 | >100 | >100 | >100 | n.d. |
Gentamicin | 1.16 ± 0.38 | 2.02 ± 0.66 | 3.97 ± 2.35 | 5.07 ± 0.14 | n.d. |
Rifampicin | n.d. * | n.d. | n.d. | n.d. | 2.4 ± 1.5 |
Scheme Treatment | Treatment Period | Efficacy |
---|---|---|
Isoniazid monotherapy | 6–9 months | 90% |
Rifampicin monotherapy | 4 months | ~90% |
Isoniazid and Rifampicin | 3–4 months | n.p. |
Isoniazid and Rifapentine | 3 months | n.p. |
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Campos, D.L.; Demarqui, F.M.; Solcia, M.C.; de Souza, P.C.; da Silva Maia, P.I.; Deflon, V.M.; Pavan, F.R. Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria. Biomedicines 2022, 10, 2398. https://doi.org/10.3390/biomedicines10102398
Campos DL, Demarqui FM, Solcia MC, de Souza PC, da Silva Maia PI, Deflon VM, Pavan FR. Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria. Biomedicines. 2022; 10(10):2398. https://doi.org/10.3390/biomedicines10102398
Chicago/Turabian StyleCampos, Débora Leite, Fernanda Manaia Demarqui, Mariana Cristina Solcia, Paula Carolina de Souza, Pedro Ivo da Silva Maia, Victor Marcelo Deflon, and Fernando Rogério Pavan. 2022. "Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria" Biomedicines 10, no. 10: 2398. https://doi.org/10.3390/biomedicines10102398