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Nucleoside analogues for the treatment of animal trypanosomiasis
Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity and drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for the treatment of AT. Promising hits were...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9111543/ https://www.ncbi.nlm.nih.gov/pubmed/35567803 http://dx.doi.org/10.1016/j.ijpddr.2022.05.001 |
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author | Mabille, Dorien Ilbeigi, Kayhan Hendrickx, Sarah Ungogo, Marzuq A. Hulpia, Fabian Lin, Cai Maes, Louis de Koning, Harry P. Van Calenbergh, Serge Caljon, Guy |
author_facet | Mabille, Dorien Ilbeigi, Kayhan Hendrickx, Sarah Ungogo, Marzuq A. Hulpia, Fabian Lin, Cai Maes, Louis de Koning, Harry P. Van Calenbergh, Serge Caljon, Guy |
author_sort | Mabille, Dorien |
collection | PubMed |
description | Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity and drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for the treatment of AT. Promising hits were identified with excellent in vitro activity across all important animal trypanosome species. Compound 7, an inosine analogue, and our previously described lead compound, 3′-deoxytubercidin (8), showed broad spectrum anti-AT activity, metabolic stability in the target host species and absence of toxicity, but with variable efficacy ranging from limited activity to full cure in mouse models of Trypanosoma congolense and T. vivax infection. Several compounds show promise against T. evansi (surra) and T. equiperdum (dourine). Given the preferred target product profile for a broad-spectrum compound against AT, this study emphasizes the need to include T. vivax in the screening cascade given its divergent susceptibility profile and provides a basis for lead optimization towards such broad spectrum anti-AT compound. |
format | Online Article Text |
id | pubmed-9111543 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-91115432022-05-18 Nucleoside analogues for the treatment of animal trypanosomiasis Mabille, Dorien Ilbeigi, Kayhan Hendrickx, Sarah Ungogo, Marzuq A. Hulpia, Fabian Lin, Cai Maes, Louis de Koning, Harry P. Van Calenbergh, Serge Caljon, Guy Int J Parasitol Drugs Drug Resist Regular article Animal trypanosomiasis (AT) is a parasitic disease with high socio-economic impact. Given the limited therapeutic options and problems of toxicity and drug resistance, this study assessed redirecting our previously identified antitrypanosomal nucleosides for the treatment of AT. Promising hits were identified with excellent in vitro activity across all important animal trypanosome species. Compound 7, an inosine analogue, and our previously described lead compound, 3′-deoxytubercidin (8), showed broad spectrum anti-AT activity, metabolic stability in the target host species and absence of toxicity, but with variable efficacy ranging from limited activity to full cure in mouse models of Trypanosoma congolense and T. vivax infection. Several compounds show promise against T. evansi (surra) and T. equiperdum (dourine). Given the preferred target product profile for a broad-spectrum compound against AT, this study emphasizes the need to include T. vivax in the screening cascade given its divergent susceptibility profile and provides a basis for lead optimization towards such broad spectrum anti-AT compound. Elsevier 2022-05-06 /pmc/articles/PMC9111543/ /pubmed/35567803 http://dx.doi.org/10.1016/j.ijpddr.2022.05.001 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular article Mabille, Dorien Ilbeigi, Kayhan Hendrickx, Sarah Ungogo, Marzuq A. Hulpia, Fabian Lin, Cai Maes, Louis de Koning, Harry P. Van Calenbergh, Serge Caljon, Guy Nucleoside analogues for the treatment of animal trypanosomiasis |
title | Nucleoside analogues for the treatment of animal trypanosomiasis |
title_full | Nucleoside analogues for the treatment of animal trypanosomiasis |
title_fullStr | Nucleoside analogues for the treatment of animal trypanosomiasis |
title_full_unstemmed | Nucleoside analogues for the treatment of animal trypanosomiasis |
title_short | Nucleoside analogues for the treatment of animal trypanosomiasis |
title_sort | nucleoside analogues for the treatment of animal trypanosomiasis |
topic | Regular article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9111543/ https://www.ncbi.nlm.nih.gov/pubmed/35567803 http://dx.doi.org/10.1016/j.ijpddr.2022.05.001 |
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