Artículo

Sepúlveda, C.S.; Fascio, M.L.; Mazzucco, M.B.; Docampo Palacios, M.L.; Pellón, R.F.; García, C.C.; D'Accorso, N.B.; Damonte, E.B. "Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses" (2008) Antiviral Chemistry and Chemotherapy. 19(1):41-47
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Abstract:

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.

Registro:

Documento: Artículo
Título:Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
Autor:Sepúlveda, C.S.; Fascio, M.L.; Mazzucco, M.B.; Docampo Palacios, M.L.; Pellón, R.F.; García, C.C.; D'Accorso, N.B.; Damonte, E.B.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Pabellón 2, 1428 Buenos Aires, Argentina
CIHIDECAR (CONICET), Departamento de Química Orgánica, Pabellón 2, 1428 Buenos Aires, Argentina
Centro de Química Farmacéutica, Apartado 16042, 11600 La Habana, Cuba
Palabras clave:10 allyl 2 fluor 9(10h) acridone; 10 allyl 6 chloro 2 fluor 9(10h) acridone; 10 allyl 7 chloro 9(10h) acridone; 6 chloro 10 (3 methyl 2 butenyl) 9(10h) acridone; acridone derivative; antivirus agent; acridone derivative; antivirus agent; animal cell; antiviral activity; Arenavirus; article; controlled study; cytotoxicity; Dengue virus; drug screening; drug structure; drug synthesis; Junin virus; nonhuman; priority journal; serotype; substitution reaction; virogenesis; virus inactivation; virus inhibition; virus strain; animal; cell survival; Cercopithecus; dengue; Dengue virus; drug effect; Junin virus; synthesis; Vero cell; virus culture; virus infection; Acridones; Animals; Antiviral Agents; Arenaviridae Infections; Cell Survival; Cercopithecus aethiops; Dengue Hemorrhagic Fever; Dengue Virus; Junin virus; Plaque Assay; Vero Cells
Año:2008
Volumen:19
Número:1
Página de inicio:41
Página de fin:47
DOI: http://dx.doi.org/10.1177/095632020801900106
Título revista:Antiviral Chemistry and Chemotherapy
Título revista abreviado:Antiviral Chem. Chemother.
ISSN:09563202
CODEN:ACCHE
CAS:Acridones; Antiviral Agents
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09563202_v19_n1_p41_Sepulveda

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Citas:

---------- APA ----------
Sepúlveda, C.S., Fascio, M.L., Mazzucco, M.B., Docampo Palacios, M.L., Pellón, R.F., García, C.C., D'Accorso, N.B.,..., Damonte, E.B. (2008) . Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses. Antiviral Chemistry and Chemotherapy, 19(1), 41-47.
http://dx.doi.org/10.1177/095632020801900106
---------- CHICAGO ----------
Sepúlveda, C.S., Fascio, M.L., Mazzucco, M.B., Docampo Palacios, M.L., Pellón, R.F., García, C.C., et al. "Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses" . Antiviral Chemistry and Chemotherapy 19, no. 1 (2008) : 41-47.
http://dx.doi.org/10.1177/095632020801900106
---------- MLA ----------
Sepúlveda, C.S., Fascio, M.L., Mazzucco, M.B., Docampo Palacios, M.L., Pellón, R.F., García, C.C., et al. "Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses" . Antiviral Chemistry and Chemotherapy, vol. 19, no. 1, 2008, pp. 41-47.
http://dx.doi.org/10.1177/095632020801900106
---------- VANCOUVER ----------
Sepúlveda, C.S., Fascio, M.L., Mazzucco, M.B., Docampo Palacios, M.L., Pellón, R.F., García, C.C., et al. Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses. Antiviral Chem. Chemother. 2008;19(1):41-47.
http://dx.doi.org/10.1177/095632020801900106