5° SEMINARIO QUÍMICA ORGÁNICA IQUIR 2021

SEMINARIO QUÍMICA ORGÁNICA 17-05-21

EXPOSITOR: Lic. Gabriel Di Gresia

TÍTULO: "Synthesis and evaluation of 3'-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents"

FUENTE: Bouton J., Furquim d’Almeida A., Maes L. , Caljon G., Van Calenbergh S., Hulpia F. European Journal of Medicinal Chemistry 216 (2021) 113290.

https://doi.org/10.1016/j.ejmech.2021.113290

DÍA, HORA y LUGAR: Lunes 17 de mayo de 2021, 18:00 h, Plataforma MEET GOOGLE.

Link: meet.google.com/bfh-poxv-bso

RESUMEN: 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.