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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320722000070 |
| _version_ | 1811343413191114752 |
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| author | Dorien Mabille Kayhan Ilbeigi Sarah Hendrickx Marzuq A. Ungogo Fabian Hulpia Cai Lin Louis Maes Harry P. de Koning Serge Van Calenbergh Guy Caljon |
| author_facet | Dorien Mabille Kayhan Ilbeigi Sarah Hendrickx Marzuq A. Ungogo Fabian Hulpia Cai Lin Louis Maes Harry P. de Koning Serge Van Calenbergh Guy Caljon |
| author_sort | Dorien Mabille |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T19:29:00Z |
| format | Article |
| id | doaj.art-67220a1220024591ad64ccc816d06c7e |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-04-13T19:29:00Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-67220a1220024591ad64ccc816d06c7e2022-12-22T02:33:15ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072022-08-01192130Nucleoside analogues for the treatment of animal trypanosomiasisDorien Mabille0Kayhan Ilbeigi1Sarah Hendrickx2Marzuq A. Ungogo3Fabian Hulpia4Cai Lin5Louis Maes6Harry P. de Koning7Serge Van Calenbergh8Guy Caljon9Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, BelgiumLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, BelgiumLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, BelgiumInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United KingdomLaboratory for Medicinal Chemistry, Ghent University, Ghent, BelgiumLaboratory for Medicinal Chemistry, Ghent University, Ghent, BelgiumLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, BelgiumInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United KingdomLaboratory for Medicinal Chemistry, Ghent University, Ghent, BelgiumLaboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2211320722000070Animal trypanosomiasisNucleoside analogues |
| spellingShingle | Dorien Mabille Kayhan Ilbeigi Sarah Hendrickx Marzuq A. Ungogo Fabian Hulpia Cai Lin Louis Maes Harry P. de Koning Serge Van Calenbergh Guy Caljon Nucleoside analogues for the treatment of animal trypanosomiasis International Journal for Parasitology: Drugs and Drug Resistance Animal trypanosomiasis Nucleoside analogues |
| 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 | Animal trypanosomiasis Nucleoside analogues |
| url | http://www.sciencedirect.com/science/article/pii/S2211320722000070 |
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