Antiamoebic Activities of Indolocarbazole Metabolites Isolated from Streptomyces sanyensis Cultures
Abstract
:1. Introduction
2. Results and Discussion
2.1. Strain Isolation, Culture, and Identification of Indolocarbazol Metabolites
2.2. Anti-Acanthamoeba Activity on Parasite Trophozoites
2.3. Cytotoxicity Assays in Murine Macrophages
2.4. In Vitro Activity against Acanthamoeba castellanii Neff Cysts
2.5. Evaluation of the Mechanism of Action of 7OSTS
3. Materials and Methods
3.1. General Experimental Procedures
3.2. Biological Material
3.3. Cultures and Preparation of Crude Extracts
3.4. Isolation of Indolocarbazole Metabolites
3.4.1. Staurosporine, (STS), (1)
3.4.2. 7-Oxostaurosporine, (7OSTS), (2)
3.4.3. 4’-Demethylamino-4′-oxostaurosporine, (4′D4′OSTS), (3)
3.4.4. Streptocarbazole B, (SCZ B), (4)
3.5. Commercial ICZ Analogs 5–7
3.6. Cell Culture
3.7. In Vitro Activity Against Acanthamoeba spp. Trophozoites
3.8. In Vitro Activity against Acanthamoeba Castellanii Neff Cysts
3.9. Cytotoxicity Test
3.10. Statistical Analysis
3.11. Double-Stain Assay for Programmed Cell Death Determination
3.12. Analysis of Mitochondrial Membrane Potential
3.13. Measurement of ATP Levels
3.14. Plasma Membrane Permeability
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compounds | A. castellanii Neff | A. griffini | A. polyphaga |
---|---|---|---|
STS (1) [18] | 0.57 ± 0.12 | 0.97± 0.12 | 2.25 ± 0.42 |
7OSTS (2) | 0.83 ± 0.09 | 0.96 ± 0.19 | 5.51 ± 0.09 |
4’D4’OSTS (3) | 7.53 ± 0.73 | 23.86 ± 0.55 | >40 |
ICZ B (4) | 6.83 ± 2.60 | 14.51 ±0.38 | >40 |
Rebeccamycin (5) | 5.37 ± 0.23 | 5.02 ± 0.18 | 7.47 ± 0.61 |
K252c (6) | 6.17 ± 0.73 | 2.25 ± 0.32 | 5.59 ± 0.34 |
Arcyriaflavin A (7) | 7.32 ± 0.45 | 7.53 ± 1.11 | 7.59 ± 0.73 |
Chlorhexidine * | 3.02 ± 0.89 | 3.73 ± 0.98 | 4.76 ± 0.08 |
Voriconazole * | 0.94 ± 0.29 | 0.10 ± 0.02 | 10.10 ± 2.21 |
Compounds | Macrophage J774A.1 CC50 (µM) |
---|---|
STS (1) | 8.74 ± 0.72 |
7OSTS (2) | 5.20 ± 1.75 |
4’D4’OSTS (3) | >40 |
ICZ B (4) | >40 |
Chlorhexidine * | 7.40 ± 0.39 |
Voriconazole * | 7.56 ± 0.77 |
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Cartuche, L.; Reyes-Batlle, M.; Sifaoui, I.; Arberas-Jiménez, I.; Piñero, J.E.; Fernández, J.J.; Lorenzo-Morales, J.; Díaz-Marrero, A.R. Antiamoebic Activities of Indolocarbazole Metabolites Isolated from Streptomyces sanyensis Cultures. Mar. Drugs 2019, 17, 588. https://doi.org/10.3390/md17100588
Cartuche L, Reyes-Batlle M, Sifaoui I, Arberas-Jiménez I, Piñero JE, Fernández JJ, Lorenzo-Morales J, Díaz-Marrero AR. Antiamoebic Activities of Indolocarbazole Metabolites Isolated from Streptomyces sanyensis Cultures. Marine Drugs. 2019; 17(10):588. https://doi.org/10.3390/md17100588
Chicago/Turabian StyleCartuche, Luis, María Reyes-Batlle, Ines Sifaoui, Iñigo Arberas-Jiménez, José E. Piñero, José J. Fernández, Jacob Lorenzo-Morales, and Ana R. Díaz-Marrero. 2019. "Antiamoebic Activities of Indolocarbazole Metabolites Isolated from Streptomyces sanyensis Cultures" Marine Drugs 17, no. 10: 588. https://doi.org/10.3390/md17100588