Publication
Title
Discovery of novel 7-aryl 7-deazapurine 3′-deoxy-ribofuranosyl nucleosides with potent activity against Trypanosoma cruzi
Author
Abstract
Chagas disease is the leading cause of cardiac-related mortality in Latin American countries where it is endemic. Trypanosoma cruzi, the disease-causing pathogen, is unable to synthesize purines de novo, necessitating salvage of preformed host purines. Therefore, purine and purine-nucleoside analogues might constitute an attractive source for identifying antitrypanosomal hits. In this study, structural elements of two purine-nucleoside analogues (i.e., cordycepin and a recently discovered 7-substituted 7-deazaadenosine) led to the identification of novel nucleoside analogues with potent in vitro activity. The structureactivity relationships of substituents at C-7 were investigated, ultimately leading to the selection of compound 5, with a C-7 para-chlorophenyl group, for in vivo evaluation. This derivative showed complete suppression of T. cruzi Y-strain blood parasitemia when orally administered twice daily for 5 days at 25 mg/kg and was able to protect infected mice from parasite-induced mortality. However, sterile cure by immunosuppression could not be demonstrated.
Language
English
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Publication
Washington, D.C. : 2018
ISSN
0022-2623 [print]
1520-4804 [online]
Volume/pages
61 :20 (2018) , p. 9287-9300
ISI
000448754900020
Pubmed ID
30234983
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Project info
Veterinary and human parasitology.
Modified 7-deazapurine nucleoside analogues for the treatment of human African trypanosomiasis: towards a strong proof-of-concept.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 29.10.2018
Last edited 21.10.2021
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