Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships
Abstract
:1. Introduction
2. Results and Discussion
IC50 (g/mL) a CI95% | CC50 (μg/mL) b CI95% | SI | ||||
Compounds | L. infantum | L. infantum | T. cruzi | NCTC | AMAc | TRYd |
Promastigotes | Amastigotes | Trypomastigotes | ||||
1 | NA | 66.51 (47.68–92.79) | NA | >200 | >3 | – |
1a | NA | NA | 20.18 (16.70–24.39) | 69.50 (64.01–75.45) | – | 3.4 |
1b | NA | NA | 17.64 (15.97-19.50) | 76.39 (70.02-83.33) | – | 4.3 |
1c | NA | NA | NA | >200 | – | – |
2 | NA | 64.90 (41.48–101.50) | 15.75 (9.80–25.30) | 96.48 (77.38–120.30) | 1.5 | 6.1 |
2a | NA | 97.59 (89.82–106.00) | 29.59 (25.61–34.18) | 95.49 (65.22–139.80) | 1.0 | 3.2 |
2b | NA | NA | 58.36 (42.82–79.55) | 69.31 (38.74–82.64) | – | 1.1 |
2c | NA | NA | 49.20 (41.69–58.05) | 57.78 (56.10–59.52) | – | 1.2 |
2d | NA | NA | NA | >200 | – | – |
3 | 57.82 (54.01–61.91) | 28.95 (19.87–42.16) | 16.28 (8.94–29.60) | 69.50 (64.01–75.45) | 2.4 | 4.3 |
3a | NA | NA | NA | >200 | – | – |
3b | NA | NA | NA | >200 | – | – |
miltefosine | 6.87 | 7.25 | – | 49.72 | – | – |
benznidazole | – | – | 114.68 | – | – | – |
T. cruzi (Trypomastigotes) | L. infantum (Amastigotes) | NCTC | |||||||
---|---|---|---|---|---|---|---|---|---|
Compounds | Experimental | Train | Validation | Experimental | Train | Validation | Experimental | Train | Validation |
1 | I | I | I | A | A | A | I | I | I |
2 | A | A | A | A | A | A | I | I | I |
2a | A | A | A | A | I | I | I | I | I |
1a | A | A | A | I | A | A | A | A | A |
1b | A | A | A | I | I | I | A | A | I |
2b | A | A | A | I | I | I | I | I | I |
2d | I | I | A | I | I | I | I | I | A |
3 | A | A | A | A | A | A | A | A | A |
1c | I | I | I | I | I | I | I | I | A |
2c | A | A | A | I | I | I | I | I | I |
3a | A | A | A | I | I | I | I | I | I |
3b | A | A | A | I | I | I | I | I | I |
3. Experimental
3.1. General Experimental Procedures
3.2. Plant Material
3.3. Extraction and Isolation of Natural Triterpenoids 1–3
3.4. Preparation of Semi-Synthetic Compounds
3.4.1. Reduction of the Carbonyl Group at C-3 (Compounds 1 and 2)
3.4.2. Hydrogenation of Δ24 (Compounds 1, 1a, 2b)
3.4.3. Acetylation of Hydroxyl Group at C-3 (Compounds 2a and 3a)
3.4.4. Methylation of Carboxylic Acid (Compounds 2 and 3)
3.5. Bioassay Procedures
3.6. Parasite Maintenance
3.7. Mammalian Cells
3.8. Determination of the Activity Against L. infantum-Promastigotes.
3.9. Determination of the Activity Against L. infantum-Intracellular Amastigotes
3.10. Determination of the Activity Against Trypanosoma cruzi-Trypomastigotes
3.11. Determination of the Cytotoxicity Against Mammalian Cells
3.12. Statistical Analysis
3.13. Molecular Interaction Fields (MIF)
3.14. Decision Tree
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Morais, T.R.; Da Costa-Silva, T.A.; Tempone, A.G.; Borborema, S.E.T.; Scotti, M.T.; De Sousa, R.M.F.; Araujo, A.C.C.; De Oliveira, A.; De Morais, S.A.L.; Sartorelli, P.; et al. Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships. Molecules 2014, 19, 5761-5776. https://doi.org/10.3390/molecules19055761
Morais TR, Da Costa-Silva TA, Tempone AG, Borborema SET, Scotti MT, De Sousa RMF, Araujo ACC, De Oliveira A, De Morais SAL, Sartorelli P, et al. Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships. Molecules. 2014; 19(5):5761-5776. https://doi.org/10.3390/molecules19055761
Chicago/Turabian StyleMorais, Thiago R., Thais A. Da Costa-Silva, Andre G. Tempone, Samanta Etel T. Borborema, Marcus T. Scotti, Raquel Maria F. De Sousa, Ana Carolina C. Araujo, Alberto De Oliveira, Sérgio Antônio L. De Morais, Patricia Sartorelli, and et al. 2014. "Antiparasitic Activity of Natural and Semi-Synthetic Tirucallane Triterpenoids from Schinus terebinthifolius (Anacardiaceae): Structure/Activity Relationships" Molecules 19, no. 5: 5761-5776. https://doi.org/10.3390/molecules19055761