Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen Histoplasma capsulatum
Abstract
:1. Introduction
2. Results
2.1. Kinase Inhibitor Library Screening Identifies Anti-Histoplasma Compounds
2.2. Characterization of Sorafenib and SC−1 Antifungal Properties
2.3. Effectiveness of Sorafenib and SC−1 against Intracellular H. capsulatum
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Fungal Strains and Culture
5.2. Chemical Library Screening
5.3. MIC Determination
5.4. LogP Determination
5.5. Fungistatic/Fungicidal Testing
5.6. Macrophage Lysis Assay
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Library | Compound | Hc WU15 | Hc WU8 | C. neoformans | C. albicans | Log P | Satisfies Lipinski’s Rule of 5? |
---|---|---|---|---|---|---|---|
GW770249A | 0.5 | 2.0 | >50 | >50 | 3.65 | Yes | |
PKIS | GW7788994X | 0.25 | 1.0 | >50 | >50 | 1.21 | Yes |
GW795486X | 2.0 | 4.0 | >50 | >50 | 4.41 | Yes | |
GW5074 | 2.0 | 4.0 | >50 | >50 | 5.31 | Partially | |
SelleckChem | Sorafenib tosylate | 1.0 | 2.0 | 25 | >50 | 3.76 | Yes |
Sorafenib | 1.0 | 2.0 | 25 | >50 | 3.8 | Yes | |
- | SC-1 | 0.25 | 1.0 | 12.5 | >50 | 5.56 | Partially |
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Berkes, C.; Franco, J.; Lawson, M.; Brann, K.; Mermelstein, J.; Laverty, D.; Connors, A. Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen Histoplasma capsulatum. Antibiotics 2021, 10, 1223. https://doi.org/10.3390/antibiotics10101223
Berkes C, Franco J, Lawson M, Brann K, Mermelstein J, Laverty D, Connors A. Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen Histoplasma capsulatum. Antibiotics. 2021; 10(10):1223. https://doi.org/10.3390/antibiotics10101223
Chicago/Turabian StyleBerkes, Charlotte, Jimmy Franco, Maxx Lawson, Katelynn Brann, Jessica Mermelstein, Daniel Laverty, and Allison Connors. 2021. "Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal Pathogen Histoplasma capsulatum" Antibiotics 10, no. 10: 1223. https://doi.org/10.3390/antibiotics10101223