Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin
- Autores
- Glisoni, Romina Julieta; Cuestas, María Luján; Mathet, Veronica Lidia; Oubiña, Jose Raul; Moglioni, Albertina Gladys; Sosnik, Alejandro Dario
- Año de publicación
- 2012
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1- indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β- cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models.
Fil: Glisoni, Romina Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuestas, María Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mathet, Veronica Lidia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Oubiña, Jose Raul. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Moglioni, Albertina Gladys. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
1-INDANONE THIOSEMICARBAZONES
ANTIVIRAL ACTIVITY
HCV REPLICON SYSTEMS
HEPATITIS C VIRUS (HCV)
HYDROXYPROPYL-Β CYCLODEXTRIN
INCLUSION COMPLEXES - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/197940
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Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrinGlisoni, Romina JulietaCuestas, María LujánMathet, Veronica LidiaOubiña, Jose RaulMoglioni, Albertina GladysSosnik, Alejandro Dario1-INDANONE THIOSEMICARBAZONESANTIVIRAL ACTIVITYHCV REPLICON SYSTEMSHEPATITIS C VIRUS (HCV)HYDROXYPROPYL-Β CYCLODEXTRININCLUSION COMPLEXEShttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1- indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β- cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models.Fil: Glisoni, Romina Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuestas, María Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mathet, Veronica Lidia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Oubiña, Jose Raul. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moglioni, Albertina Gladys. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2012-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197940Glisoni, Romina Julieta; Cuestas, María Luján; Mathet, Veronica Lidia; Oubiña, Jose Raul; Moglioni, Albertina Gladys; et al.; Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin; Elsevier Science; European Journal of Pharmaceutical Sciences; 47; 3; 10-2012; 596-6030928-0987CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0928098712002965info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejps.2012.07.018info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:23Zoai:ri.conicet.gov.ar:11336/197940instacron: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:34982025-09-03 10:11:24.188CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
title |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
spellingShingle |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin Glisoni, Romina Julieta 1-INDANONE THIOSEMICARBAZONES ANTIVIRAL ACTIVITY HCV REPLICON SYSTEMS HEPATITIS C VIRUS (HCV) HYDROXYPROPYL-Β CYCLODEXTRIN INCLUSION COMPLEXES |
title_short |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
title_full |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
title_fullStr |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
title_full_unstemmed |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
title_sort |
Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin |
dc.creator.none.fl_str_mv |
Glisoni, Romina Julieta Cuestas, María Luján Mathet, Veronica Lidia Oubiña, Jose Raul Moglioni, Albertina Gladys Sosnik, Alejandro Dario |
author |
Glisoni, Romina Julieta |
author_facet |
Glisoni, Romina Julieta Cuestas, María Luján Mathet, Veronica Lidia Oubiña, Jose Raul Moglioni, Albertina Gladys Sosnik, Alejandro Dario |
author_role |
author |
author2 |
Cuestas, María Luján Mathet, Veronica Lidia Oubiña, Jose Raul Moglioni, Albertina Gladys Sosnik, Alejandro Dario |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
1-INDANONE THIOSEMICARBAZONES ANTIVIRAL ACTIVITY HCV REPLICON SYSTEMS HEPATITIS C VIRUS (HCV) HYDROXYPROPYL-Β CYCLODEXTRIN INCLUSION COMPLEXES |
topic |
1-INDANONE THIOSEMICARBAZONES ANTIVIRAL ACTIVITY HCV REPLICON SYSTEMS HEPATITIS C VIRUS (HCV) HYDROXYPROPYL-Β CYCLODEXTRIN INCLUSION COMPLEXES |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/2.10 https://purl.org/becyt/ford/2 |
dc.description.none.fl_txt_mv |
The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1- indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β- cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models. Fil: Glisoni, Romina Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cuestas, María Luján. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mathet, Veronica Lidia. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Oubiña, Jose Raul. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Área Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Moglioni, Albertina Gladys. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sosnik, Alejandro Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1- indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β- cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-10 |
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/11336/197940 Glisoni, Romina Julieta; Cuestas, María Luján; Mathet, Veronica Lidia; Oubiña, Jose Raul; Moglioni, Albertina Gladys; et al.; Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin; Elsevier Science; European Journal of Pharmaceutical Sciences; 47; 3; 10-2012; 596-603 0928-0987 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/197940 |
identifier_str_mv |
Glisoni, Romina Julieta; Cuestas, María Luján; Mathet, Veronica Lidia; Oubiña, Jose Raul; Moglioni, Albertina Gladys; et al.; Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β- cyclodextrin; Elsevier Science; European Journal of Pharmaceutical Sciences; 47; 3; 10-2012; 596-603 0928-0987 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0928098712002965 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejps.2012.07.018 |
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 |
dc.publisher.none.fl_str_mv |
Elsevier Science |
publisher.none.fl_str_mv |
Elsevier Science |
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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1842270156648087552 |
score |
13.13397 |