Synthesis and evaluation of 3'-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents.
Eur J Med Chem
; 216: 113290, 2021 Apr 15.
Article
in En
| MEDLINE
| ID: mdl-33667845
ABSTRACT
Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3'-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3'-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3'-deoxy-3'-fluororibofuranosyl and 3'-deoxy-3'-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3'-position is a promising modification for the discovery of antiparasitic nucleosides.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Purine Nucleosides
/
Purines
/
Trypanocidal Agents
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2021
Document type:
Article
Affiliation country:
Bélgica