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

Autores
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
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Mazzucco, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Docampo Palacios, Maite L.. Centro de Química Farmacéutica; Argentina
Fil: Pellón, Rolando F.. Centro de Química Farmacéutica; Argentina
Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Materia
Junin Virus
Dengue Virus
Hemorrhagic Fever Viruses
Acridones
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/71284
Acceder
id CONICETDig_7fb0eef23ee2652f9d9dfbc4f9aebade
oai_identifier_str oai:ri.conicet.gov.ar:11336/71284
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever virusesSepúlveda, Claudia SoledadFascio, Mirta LilianaMazzucco, María BelénDocampo Palacios, Maite L.Pellón, Rolando F.Garcia, CybeleD'accorso, Norma BeatrizDamonte, Elsa BeatrizJunin VirusDengue VirusHemorrhagic Fever VirusesAcridoneshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: 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.Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Mazzucco, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Docampo Palacios, Maite L.. Centro de Química Farmacéutica; ArgentinaFil: Pellón, Rolando F.. Centro de Química Farmacéutica; ArgentinaFil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaInternational Medical Press2008-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/71284Sepúlveda, 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; 41-470956-3202CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1177/095632020801900106info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/095632020801900106info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:20Zoai:ri.conicet.gov.ar:11336/71284instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:56:20.704CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
title Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
spellingShingle Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
Sepúlveda, Claudia Soledad
Junin Virus
Dengue Virus
Hemorrhagic Fever Viruses
Acridones
title_short Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
title_full Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
title_fullStr Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
title_full_unstemmed Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
title_sort Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
dc.creator.none.fl_str_mv 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
author Sepúlveda, Claudia Soledad
author_facet 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
author_role author
author2 Fascio, Mirta Liliana
Mazzucco, María Belén
Docampo Palacios, Maite L.
Pellón, Rolando F.
Garcia, Cybele
D'accorso, Norma Beatriz
Damonte, Elsa Beatriz
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Junin Virus
Dengue Virus
Hemorrhagic Fever Viruses
Acridones
topic Junin Virus
Dengue Virus
Hemorrhagic Fever Viruses
Acridones
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Sepúlveda, Claudia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Mazzucco, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Docampo Palacios, Maite L.. Centro de Química Farmacéutica; Argentina
Fil: Pellón, Rolando F.. Centro de Química Farmacéutica; Argentina
Fil: Garcia, Cybele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
description 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.
publishDate 2008
dc.date.none.fl_str_mv 2008-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/71284
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
url http://hdl.handle.net/11336/71284
identifier_str_mv 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
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1177/095632020801900106
info:eu-repo/semantics/altIdentifier/url/https://journals.sagepub.com/doi/10.1177/095632020801900106
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv International Medical Press
publisher.none.fl_str_mv International Medical Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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