A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity
Abstract
:1. Introduction
2. Results
2.1. Development of a Multi-Species High Content Screening Assay
2.2. Diversity Library Screening against Leishmania Species
2.3. Identification of Pan-Active Compounds
3. Discussion
4. Methods
4.1. Reference Compounds and Library
4.2. Host Cell and Parasite Cultures
4.3. Intracellular Amastigotes Assay and Library Screening
4.4. High Content Image Acquisition and Analysis
4.5. Data Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compound CB1954 are available from the authors. |
Screening Parameters | L. amazonensis | L. braziliensis | L. donovani |
---|---|---|---|
Z’-factor | 0.65 ± 0.04 | 0.76 ± 0.07 | 0.77 ± 0.05 |
Correlation index | 0.86 | 0.88 | 0.89 |
CV of infected control (%) | 11.74 | 11.4 | 13.5 |
EC50 Amphotericin B (µM) | 2.10 ± 0.16 | 0.93 ± 0.45 | 0.82 ± 0.07 |
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Alcântara, L.M.; Ferreira, T.C.S.; Fontana, V.; Chatelain, E.; Moraes, C.B.; Freitas-Junior, L.H. A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity. Molecules 2020, 25, 2551. https://doi.org/10.3390/molecules25112551
Alcântara LM, Ferreira TCS, Fontana V, Chatelain E, Moraes CB, Freitas-Junior LH. A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity. Molecules. 2020; 25(11):2551. https://doi.org/10.3390/molecules25112551
Chicago/Turabian StyleAlcântara, Laura M., Thalita C. S. Ferreira, Vanessa Fontana, Eric Chatelain, Carolina B. Moraes, and Lucio H. Freitas-Junior. 2020. "A Multi-Species Phenotypic Screening Assay for Leishmaniasis Drug Discovery Shows That Active Compounds Display a High Degree of Species-Specificity" Molecules 25, no. 11: 2551. https://doi.org/10.3390/molecules25112551