Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhe...

Autores
Soraires Santacruz, Maria Cristina; Fabiani, Matias; Castro, Eliana Florencia; Cavallaro, Lucia Vicenta; Finkielsztein, Liliana Mónica
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A series of N4-arylsubstituted thiosemicarbazones derived from 1-indanones and a set of compounds lacking such substitution in the N4 position of the thiosemicarbazone moiety were synthesized and evaluated for their anti-bovine viral diarrhea virus (BVDV) activity. Among these, derivatives 2 and 15 displayed high activity (EC50 = 2.7 ± 0.4 and 0.7 ± 0.1 µM, respectively) as inhibitors of BVDV replication. Novel key structural features related to the anti-BVDV activity were identified by structure-activity relationship (SAR) analysis. In a previous study, the thiosemicarbazone of 5,6-dimethoxy-1-indanone (5,6-TSC) was characterized as a non-nucleoside inhibitor (NNI) of the BVDV RNA-dependent RNA polymerase. In the present work, cross-resistance assays were performed with the most active compounds. Such studies were carried out on 5,6-TSC resistant BVDV (BVDV-TSCr T1) carrying mutations in the viral polymerase. This BVDV mutant was also resistant to compound 15. Molecular docking studies and MM/PBSA calculations were performed to assess the most active derivatives at the 5,6-TSC viral polymerase binding site. The differences in the interaction pattern and the binding affinity of derivative 15 either to the wild type or BVDV-TSCr T1 polymerase were key factors to define the mode of action of this compound.
Fil: Soraires Santacruz, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Fabiani, Matias. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Castro, Eliana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cavallaro, Lucia Vicenta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Finkielsztein, Liliana Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Materia
Thiosemicarbazones
Bovine Viral Diarrhea Virus (Bvdv)
Rna-Dependent Rna Polymerase
Molecular Docking
Antiviral Activity
Antiviral Resistance
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47837
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47837
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agentsSoraires Santacruz, Maria CristinaFabiani, MatiasCastro, Eliana FlorenciaCavallaro, Lucia VicentaFinkielsztein, Liliana MónicaThiosemicarbazonesBovine Viral Diarrhea Virus (Bvdv)Rna-Dependent Rna PolymeraseMolecular DockingAntiviral ActivityAntiviral Resistancehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A series of N4-arylsubstituted thiosemicarbazones derived from 1-indanones and a set of compounds lacking such substitution in the N4 position of the thiosemicarbazone moiety were synthesized and evaluated for their anti-bovine viral diarrhea virus (BVDV) activity. Among these, derivatives 2 and 15 displayed high activity (EC50 = 2.7 ± 0.4 and 0.7 ± 0.1 µM, respectively) as inhibitors of BVDV replication. Novel key structural features related to the anti-BVDV activity were identified by structure-activity relationship (SAR) analysis. In a previous study, the thiosemicarbazone of 5,6-dimethoxy-1-indanone (5,6-TSC) was characterized as a non-nucleoside inhibitor (NNI) of the BVDV RNA-dependent RNA polymerase. In the present work, cross-resistance assays were performed with the most active compounds. Such studies were carried out on 5,6-TSC resistant BVDV (BVDV-TSCr T1) carrying mutations in the viral polymerase. This BVDV mutant was also resistant to compound 15. Molecular docking studies and MM/PBSA calculations were performed to assess the most active derivatives at the 5,6-TSC viral polymerase binding site. The differences in the interaction pattern and the binding affinity of derivative 15 either to the wild type or BVDV-TSCr T1 polymerase were key factors to define the mode of action of this compound.Fil: Soraires Santacruz, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaFil: Fabiani, Matias. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Castro, Eliana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Cavallaro, Lucia Vicenta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Finkielsztein, Liliana Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; ArgentinaPergamon-Elsevier Science Ltd2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47837Soraires Santacruz, Maria Cristina; Fabiani, Matias; Castro, Eliana Florencia; Cavallaro, Lucia Vicenta; Finkielsztein, Liliana Mónica; Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 25; 15; 5-2017; 4055-40630968-0896CONICET DigitalCONICETenghttp://hdl.handle.net/11336/157314info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2017.05.056info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0968089617304327info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:31:56Zoai:ri.conicet.gov.ar:11336/47837instacron: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:34982025-10-15 14:31:56.852CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
title Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
spellingShingle Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
Soraires Santacruz, Maria Cristina
Thiosemicarbazones
Bovine Viral Diarrhea Virus (Bvdv)
Rna-Dependent Rna Polymerase
Molecular Docking
Antiviral Activity
Antiviral Resistance
title_short Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
title_full Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
title_fullStr Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
title_full_unstemmed Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
title_sort Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents
dc.creator.none.fl_str_mv Soraires Santacruz, Maria Cristina
Fabiani, Matias
Castro, Eliana Florencia
Cavallaro, Lucia Vicenta
Finkielsztein, Liliana Mónica
author Soraires Santacruz, Maria Cristina
author_facet Soraires Santacruz, Maria Cristina
Fabiani, Matias
Castro, Eliana Florencia
Cavallaro, Lucia Vicenta
Finkielsztein, Liliana Mónica
author_role author
author2 Fabiani, Matias
Castro, Eliana Florencia
Cavallaro, Lucia Vicenta
Finkielsztein, Liliana Mónica
author2_role author
author
author
author
dc.subject.none.fl_str_mv Thiosemicarbazones
Bovine Viral Diarrhea Virus (Bvdv)
Rna-Dependent Rna Polymerase
Molecular Docking
Antiviral Activity
Antiviral Resistance
topic Thiosemicarbazones
Bovine Viral Diarrhea Virus (Bvdv)
Rna-Dependent Rna Polymerase
Molecular Docking
Antiviral Activity
Antiviral Resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A series of N4-arylsubstituted thiosemicarbazones derived from 1-indanones and a set of compounds lacking such substitution in the N4 position of the thiosemicarbazone moiety were synthesized and evaluated for their anti-bovine viral diarrhea virus (BVDV) activity. Among these, derivatives 2 and 15 displayed high activity (EC50 = 2.7 ± 0.4 and 0.7 ± 0.1 µM, respectively) as inhibitors of BVDV replication. Novel key structural features related to the anti-BVDV activity were identified by structure-activity relationship (SAR) analysis. In a previous study, the thiosemicarbazone of 5,6-dimethoxy-1-indanone (5,6-TSC) was characterized as a non-nucleoside inhibitor (NNI) of the BVDV RNA-dependent RNA polymerase. In the present work, cross-resistance assays were performed with the most active compounds. Such studies were carried out on 5,6-TSC resistant BVDV (BVDV-TSCr T1) carrying mutations in the viral polymerase. This BVDV mutant was also resistant to compound 15. Molecular docking studies and MM/PBSA calculations were performed to assess the most active derivatives at the 5,6-TSC viral polymerase binding site. The differences in the interaction pattern and the binding affinity of derivative 15 either to the wild type or BVDV-TSCr T1 polymerase were key factors to define the mode of action of this compound.
Fil: Soraires Santacruz, Maria Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
Fil: Fabiani, Matias. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Castro, Eliana Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Cavallaro, Lucia Vicenta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Finkielsztein, Liliana Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Química Medicinal; Argentina
description A series of N4-arylsubstituted thiosemicarbazones derived from 1-indanones and a set of compounds lacking such substitution in the N4 position of the thiosemicarbazone moiety were synthesized and evaluated for their anti-bovine viral diarrhea virus (BVDV) activity. Among these, derivatives 2 and 15 displayed high activity (EC50 = 2.7 ± 0.4 and 0.7 ± 0.1 µM, respectively) as inhibitors of BVDV replication. Novel key structural features related to the anti-BVDV activity were identified by structure-activity relationship (SAR) analysis. In a previous study, the thiosemicarbazone of 5,6-dimethoxy-1-indanone (5,6-TSC) was characterized as a non-nucleoside inhibitor (NNI) of the BVDV RNA-dependent RNA polymerase. In the present work, cross-resistance assays were performed with the most active compounds. Such studies were carried out on 5,6-TSC resistant BVDV (BVDV-TSCr T1) carrying mutations in the viral polymerase. This BVDV mutant was also resistant to compound 15. Molecular docking studies and MM/PBSA calculations were performed to assess the most active derivatives at the 5,6-TSC viral polymerase binding site. The differences in the interaction pattern and the binding affinity of derivative 15 either to the wild type or BVDV-TSCr T1 polymerase were key factors to define the mode of action of this compound.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
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/11336/47837
Soraires Santacruz, Maria Cristina; Fabiani, Matias; Castro, Eliana Florencia; Cavallaro, Lucia Vicenta; Finkielsztein, Liliana Mónica; Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 25; 15; 5-2017; 4055-4063
0968-0896
CONICET Digital
CONICET
url http://hdl.handle.net/11336/47837
identifier_str_mv Soraires Santacruz, Maria Cristina; Fabiani, Matias; Castro, Eliana Florencia; Cavallaro, Lucia Vicenta; Finkielsztein, Liliana Mónica; Synthesis, antiviral evaluation and molecular docking studies of N 4 -aryl substituted/unsubstituted thiosemicarbazones derived from 1-indanones as potent anti-bovine viral diarrhea virus agents; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 25; 15; 5-2017; 4055-4063
0968-0896
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv http://hdl.handle.net/11336/157314
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bmc.2017.05.056
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0968089617304327
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
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 13.22299

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