Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever
Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria par...
| Autores principales: | , , , , , |
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| Formato: | Journal Article |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2019
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| Materias: | |
| Acceso en línea: | https://hdl.handle.net/10568/99526 |
| _version_ | 1855539156774551552 |
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| author | Nyagwange, James Awino, Elias Tijhaar, Edwin Svitek, Nicholas Pelle, Roger Nene, Vishvanath M. |
| author_browse | Awino, Elias Nene, Vishvanath M. Nyagwange, James Pelle, Roger Svitek, Nicholas Tijhaar, Edwin |
| author_facet | Nyagwange, James Awino, Elias Tijhaar, Edwin Svitek, Nicholas Pelle, Roger Nene, Vishvanath M. |
| author_sort | Nyagwange, James |
| collection | Repository of Agricultural Research Outputs (CGSpace) |
| description | Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T. parva. Using a 3H-thymidine incorporation assay we screened 796 open source compounds from the Medicines for Malaria Venture (MMV) to discover novel chemicals with potential inhibitory activity to T. parva. We identified nine malaria box compounds and eight pathogen box compounds that inhibited the proliferation of F100TpM, a T. parva infected lymphocyte cell line. However, only two compounds, MMV008212 and MMV688372 represent promising leads with IC50 values of 0.78 and 0.61 μM, respectively, and CC50 values > 5 μM. The remaining compounds exhibited a high degree of toxicity (CC50 values < 1.09 μM) on the proliferation of bovine peripheral blood mononuclear cells stimulated with concanavalin A. We also tested the anti-cancer drug, dasatinib, used in the chemotherapy of some leukemias. Dasatinib was as active and safe as buparvaquone in vitro, with an IC50 of 5 and 4.2 nM, respectively, and CC50 > 10 μM. Our preliminary data suggest that it may be possible to repurpose compounds from the cancer field as well as MMV as novel anti-T. parva molecules. |
| format | Journal Article |
| id | CGSpace99526 |
| institution | CGIAR Consortium |
| language | Inglés |
| publishDate | 2019 |
| publishDateRange | 2019 |
| publishDateSort | 2019 |
| publisher | Elsevier |
| publisherStr | Elsevier |
| record_format | dspace |
| spelling | CGSpace995262024-10-03T07:40:58Z Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever Nyagwange, James Awino, Elias Tijhaar, Edwin Svitek, Nicholas Pelle, Roger Nene, Vishvanath M. theileria cattle animal diseases vaccines disease control east coast fever Chemotherapy of East Coast fever, a lymphoproliferative cancer-like disease of cattle causing significant economic losses in Africa, is largely dependent on the use of buparvaquone, a drug that was developed in the late 1980's. The disease is caused by the tick-borne protozoan pathogen Theileria parva. Buparvaquone can be used prophylactically and it is also active against tropical theileriosis, caused by the related parasite Theileria annulata. Recently, drug resistance was reported in T. annulata, and could occur in T. parva. Using a 3H-thymidine incorporation assay we screened 796 open source compounds from the Medicines for Malaria Venture (MMV) to discover novel chemicals with potential inhibitory activity to T. parva. We identified nine malaria box compounds and eight pathogen box compounds that inhibited the proliferation of F100TpM, a T. parva infected lymphocyte cell line. However, only two compounds, MMV008212 and MMV688372 represent promising leads with IC50 values of 0.78 and 0.61 μM, respectively, and CC50 values > 5 μM. The remaining compounds exhibited a high degree of toxicity (CC50 values < 1.09 μM) on the proliferation of bovine peripheral blood mononuclear cells stimulated with concanavalin A. We also tested the anti-cancer drug, dasatinib, used in the chemotherapy of some leukemias. Dasatinib was as active and safe as buparvaquone in vitro, with an IC50 of 5 and 4.2 nM, respectively, and CC50 > 10 μM. Our preliminary data suggest that it may be possible to repurpose compounds from the cancer field as well as MMV as novel anti-T. parva molecules. 2019-04 2019-02-21T13:23:31Z 2019-02-21T13:23:31Z Journal Article https://hdl.handle.net/10568/99526 en Open Access Elsevier Nyagwange, J., Awino, E., Tijhaar, E., Svitek, N., Pelle, R. and Nene, V. 2019. Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever. International Journal for Parasitology: Drugs and Drug Resistance 9:80-86. |
| spellingShingle | theileria cattle animal diseases vaccines disease control east coast fever Nyagwange, James Awino, Elias Tijhaar, Edwin Svitek, Nicholas Pelle, Roger Nene, Vishvanath M. Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title | Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title_full | Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title_fullStr | Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title_full_unstemmed | Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title_short | Leveraging the Medicines for Malaria Venture malaria and pathogen boxes to discover chemical inhibitors of East Coast fever |
| title_sort | leveraging the medicines for malaria venture malaria and pathogen boxes to discover chemical inhibitors of east coast fever |
| topic | theileria cattle animal diseases vaccines disease control east coast fever |
| url | https://hdl.handle.net/10568/99526 |
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