info:eu-repo/semantics/article
Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
Fecha
2008-12Registro en:
Sepúlveda, Claudia Soledad; Fascio, Mirta Liliana; Mazzucco, María Belén; Docampo Palacios, Maite L.; Pellón, Rolando F.; et al.; Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses; International Medical Press; Antiviral Chemistry & Chemotherapy; 19; 1; 12-2008; 41-47
0956-3202
CONICET Digital
CONICET
Autor
Sepúlveda, Claudia Soledad
Fascio, Mirta Liliana
Mazzucco, María Belén
Docampo Palacios, Maite L.
Pellón, Rolando F.
Garcia, Cybele
D'accorso, Norma Beatriz
Damonte, Elsa Beatriz
Resumen
Background: In the present study, a series of N-substituted acridone derivatives was synthesized and evaluated against two haemorrhagic fever viruses (HFV). Methods: Compounds were tested against Junin virus (JUNV), an arenavirus agent of Argentine haemorrhagic fever, and dengue virus (DENV), a flavivirus agent of the most prevalent arthropod-borne viral disease in humans. Results: Among tested compounds, two N-allyl acridones (derivatives 3c and 3f) elicited a potent and selective antiviral activity against JUNV (strain IV4454) and DENV-2 (strain NGC) with 50% effective concentration values between 2.5 and 5.5 μM, as determined by virus yield inhibition. No cytotoxicity was detected at concentrations up to 1,000 μM, resulting in selectivity indices >181.8-400.0. Both acridones were effective against a wide spectrum of arenaviruses and the four serotypes of DENV. Furthermore, 3c and 3f failed to inactivate virus before cell infection as well as to induce a refractory state by cell pretreatment, indicating that the inhibitory effect was exerted through a blockade in virus multiplication during the infectious process. Conclusion: These data are the first demonstration that acridone derivatives have a potent antiviral activity that block in vitro multiplication of HFV belonging to Arenaviridae and Flaviviridae, such as JUNV and DENV. © 2008 International Medical Press.