Nucleoside analogues for the treatment of animal trypanosomiasis

Mabille, D., Ilbeigi, K., Hendrickx, S., Ungogo, M. A., Hulpia, F., Lin, C., Maes, L., de Koning, H. P. , Van Calenbergh, S. and Caljon, G. (2022) Nucleoside analogues for the treatment of animal trypanosomiasis. International Journal for Parasitology: Drugs and Drug Resistance, 19, pp. 21-30. (doi: 10.1016/j.ijpddr.2022.05.001) (PMID:35567803) (PMCID:PMC9111543)

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 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 toward such broad spectrum anti-AT compound.

• Item Type: Articles
• Additional Information: This work was supported by the Fonds Wetenschappelijk Onderzoek (www.fwo.be; grant numbers G033618N, G013118N), the University of Antwerp (www.uantwerpen.be; grant numbers TT-ZAPBOF 33049 and IOF-PoC 42404) and the Petroleum Technology Development Fund of Nigeria (PhD scholarship to M.A.U.).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ungogo, Mr Marzuq and De Koning, Professor Harry
• Authors: Mabille, D., Ilbeigi, K., Hendrickx, S., Ungogo, M. A., Hulpia, F., Lin, C., Maes, L., de Koning, H. P., Van Calenbergh, S., and Caljon, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: International Journal for Parasitology: Drugs and Drug Resistance
• Publisher: Elsevier
• ISSN: 2211-3207
• ISSN (Online): 2211-3207
• Published Online: 06 May 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in International Journal for Parasitology: Drugs and Drug Resistance 19: 21-30
• Publisher Policy: Reproduced under a Creative Commons License