Nucleoside analogues for the treatment of animal trypanosomiasis.

Animals Disease Models, Animal Drug Resistance Mice Nucleosides / therapeutic use Trypanosoma Trypanosoma congolense Trypanosomiasis / drug therapy
Animal trypanosomiasis Nucleoside analogues

Journal

International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
Titre abrégé: Int J Parasitol Drugs Drug Resist
Pays: Netherlands
ID NLM: 101576715

Informations de publication

Date de publication:
08 2022
Historique:
received: 29 10 2021
revised: 30 04 2022
accepted: 03 05 2022
pubmed: 15 5 2022
medline: 9 8 2022
entrez: 14 5 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ijpddr.2022.05.001 PMID: 35567803 PMC: PMC9111543
pubmed: 35567803
pii: S2211-3207(22)00007-0
doi: 10.1016/j.ijpddr.2022.05.001
pmc: PMC9111543
pii:
doi:

Substances chimiques

Nucleosides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

21-30

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

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Auteurs

Dorien Mabille (D)

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium. Electronic address: dorien.mabille@uantwerpen.be.

Kayhan Ilbeigi (K)

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium. Electronic address: kayhan.ilbeigi@uantwerpen.be.

Sarah Hendrickx (S)

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium. Electronic address: sarah.hendrickx@uantwerpen.be.

Marzuq A Ungogo (MA)

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom. Electronic address: 2226184U@student.gla.ac.uk.

Fabian Hulpia (F)

Laboratory for Medicinal Chemistry, Ghent University, Ghent, Belgium. Electronic address: FHulpia@ITS.JNJ.com.

Cai Lin (C)

Laboratory for Medicinal Chemistry, Ghent University, Ghent, Belgium. Electronic address: cai.lin@ugent.be.

Louis Maes (L)

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium. Electronic address: louis.maes@uantwerpen.be.

Harry P de Koning (HP)

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, United Kingdom. Electronic address: harry.de-koning@glasgow.ac.uk.

Serge Van Calenbergh (S)

Laboratory for Medicinal Chemistry, Ghent University, Ghent, Belgium. Electronic address: serge.vancalenbergh@ugent.be.

Guy Caljon (G)

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium. Electronic address: guy.caljon@uantwerpen.be.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Eucaryotes › Euglénozoaires › Kinetoplastida › Trypanosomatina › Trypanosoma › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Eucaryotes › Euglénozoaires › Kinetoplastida › Trypanosomatina › Trypanosoma › Trypanosoma congolense › Nucleoside analogues for the treatment of...
questionsmedicales.fr › Infection › Maladies parasitaires › Protozooses › Infections à Euglenozoa › Trypanosomiase › Nucleoside analogues for the treatment of...