Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses
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 flav...
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todo:paper_09563202_v19_n1_p41_Sepulveda2023-10-03T15:51:54Z Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses 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. 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 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, C.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fascio, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:D'Accorso, N.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Damonte, E.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09563202_v19_n1_p41_Sepulveda |
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Universidad de Buenos Aires |
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I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| 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. |
| format |
JOUR |
| author |
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. |
| author_facet |
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. |
| author_sort |
Sepúlveda, C.S. |
| title |
Synthesis and evaluation of N-substituted acridones as antiviral agents against haemorrhagic fever viruses |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_09563202_v19_n1_p41_Sepulveda |
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