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Abstract
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 broadspectrum 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.
Keywords
Pharmacology (medical), Infectious Diseases, Pharmacology, Parasitology, Animal trypanosomiasis, Nucleoside analogues, DRUG-RESISTANCE, AFRICAN TRYPANOSOMIASIS, CHEMOTHERAPY, TUBERCIDIN, FEXINIDAZOLE, DIAGNOSIS, TOXICITY

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Citation

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MLA
Mabille, Dorien, et al. “Nucleoside Analogues for the Treatment of Animal Trypanosomiasis.” INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, vol. 19, 2022, pp. 21–30, doi:10.1016/j.ijpddr.2022.05.001.
APA
Mabille, D., Ilbeigi, K., Hendrickx, S., Ungogo, M. A., Hulpia, F., Lin, C., … Caljon, G. (2022). Nucleoside analogues for the treatment of animal trypanosomiasis. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, 19, 21–30. https://doi.org/10.1016/j.ijpddr.2022.05.001
Chicago author-date
Mabille, Dorien, Kayhan Ilbeigi, Sarah Hendrickx, Marzuq A. Ungogo, Fabian Hulpia, Cai Lin, Louis Maes, Harry P. de Koning, Serge Van Calenbergh, and Guy Caljon. 2022. “Nucleoside Analogues for the Treatment of Animal Trypanosomiasis.” INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE 19: 21–30. https://doi.org/10.1016/j.ijpddr.2022.05.001.
Chicago author-date (all authors)
Mabille, Dorien, Kayhan Ilbeigi, Sarah Hendrickx, Marzuq A. Ungogo, Fabian Hulpia, Cai Lin, Louis Maes, Harry P. de Koning, Serge Van Calenbergh, and Guy Caljon. 2022. “Nucleoside Analogues for the Treatment of Animal Trypanosomiasis.” INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE 19: 21–30. doi:10.1016/j.ijpddr.2022.05.001.
Vancouver
1.
Mabille D, Ilbeigi K, Hendrickx S, Ungogo MA, Hulpia F, Lin C, et al. Nucleoside analogues for the treatment of animal trypanosomiasis. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE. 2022;19:21–30.
IEEE
[1]
D. Mabille et al., “Nucleoside analogues for the treatment of animal trypanosomiasis,” INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, vol. 19, pp. 21–30, 2022.
@article{8770789,
  abstract     = {{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 broadspectrum 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.}},
  author       = {{Mabille, Dorien and Ilbeigi, Kayhan and Hendrickx, Sarah and Ungogo, Marzuq A. and Hulpia, Fabian and Lin, Cai and Maes, Louis and de Koning, Harry P. and Van Calenbergh, Serge and Caljon, Guy}},
  issn         = {{2211-3207}},
  journal      = {{INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE}},
  keywords     = {{Pharmacology (medical),Infectious Diseases,Pharmacology,Parasitology,Animal trypanosomiasis,Nucleoside analogues,DRUG-RESISTANCE,AFRICAN TRYPANOSOMIASIS,CHEMOTHERAPY,TUBERCIDIN,FEXINIDAZOLE,DIAGNOSIS,TOXICITY}},
  language     = {{eng}},
  pages        = {{21--30}},
  title        = {{Nucleoside analogues for the treatment of animal trypanosomiasis}},
  url          = {{http://doi.org/10.1016/j.ijpddr.2022.05.001}},
  volume       = {{19}},
  year         = {{2022}},
}

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