Synthesis and evaluation of N-substituted acridones as antiviral agents against hemorrhagic fever viruses.

SEPÚLVEDA CLAUDIA S.; FASCIO MIRTA L.; MAZZUCCCO MARÍA B.; DOCAMPO PALACIOS MAITE; PELLÓN ROLANDO F.; D'ACCORSO NORMA BEATRIZ; DAMONTE ELSA B.

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY

International Medical Press

Año: 2008 vol. 19 p. 41 - 47

0956-3202

In the present study, a series of N-substituted acridone derivatives was synthesized and evaluated against two hemorrhagic fever viruses (HFV): Junin virus (JUNV), an arenavirus agent of Argentine hemorrhagic fever, and dengue virus (DENV), a flavivirus agent of the most prevalent arthropod-borne viral desease in humans. 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 EC50 values in the range 2.5-5.5 µM, as determined by virus yield inhibition. No cytotoxicity was detected at concentration up to 1000 µM, resulting in selectivity indices greater than 181.8-400.0. Both acridiones were effective against a wide spectrum of arenaviruses and the four serotypes of DENV. Furthermore, 3c and 3f failed to inactive 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.