Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity

Autores
Glisoni, Romina Julieta; Chiappetta, Diego Andrés; Finkielsztein, Liliana Mónica; Moglioni, Albertina Gladys; Sosnik, Alejandro Dario
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The present work aimed to gain further insight into the mechanisms governing the aggregation process of 1-indanone thiosemicarbazone drug candidates. Regardless of the relatively low lipophilicity predicted by theoretical calculations, these compounds were very insoluble in water. This performance was especially notorious for methoxylated (and non-N-allylated) derivatives. Thermal analysis revealed that the introduction of one and two CH3O- moieties into the aromatic ring increases the Tm pronouncedly from 185 °C to 229°C and 258 °C, respectively. The formation of nano-aggregates in water was suggested by the appearance of a new strong absorption peak at 233-239 nm in the UV spectra. DLS analysis showed the early formation nanoscopic particles (120-300 nm) that undergo a gradual size growth to generate larger submicron structures; these particles remained invisible to the naked eye. The negatively-charged character of the surface was established by zeta potential measurements. These results suggest the generation of an inner hydrophobic "core" due to the interaction of highly hydrophobic aromatic rings that is surface-decorated by CS groups available in a thiolato anionic form. This aggregation mechanism is supported by the fact that methoxylation of the aromatic ring dramatically strengthens the solute-solute affinity, as expressed by the sharp increase in Tm and makes these derivatives much more water-insoluble. Finally, overall findings indicate that for these compounds, solubility predictions based on lipophilicity calculations are not reliable and a more thorough characterization is required.
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. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Materia
SELF-AGGREGATION
THIOSEMICARBAZONE
ANTIVIRAL ACTIVITY
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:11336/112987
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/112987
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activityGlisoni, Romina JulietaChiappetta, Diego AndrésFinkielsztein, Liliana MónicaMoglioni, Albertina GladysSosnik, Alejandro DarioSELF-AGGREGATIONTHIOSEMICARBAZONEANTIVIRAL ACTIVITYhttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/2The present work aimed to gain further insight into the mechanisms governing the aggregation process of 1-indanone thiosemicarbazone drug candidates. Regardless of the relatively low lipophilicity predicted by theoretical calculations, these compounds were very insoluble in water. This performance was especially notorious for methoxylated (and non-N-allylated) derivatives. Thermal analysis revealed that the introduction of one and two CH3O- moieties into the aromatic ring increases the Tm pronouncedly from 185 °C to 229°C and 258 °C, respectively. The formation of nano-aggregates in water was suggested by the appearance of a new strong absorption peak at 233-239 nm in the UV spectra. DLS analysis showed the early formation nanoscopic particles (120-300 nm) that undergo a gradual size growth to generate larger submicron structures; these particles remained invisible to the naked eye. The negatively-charged character of the surface was established by zeta potential measurements. These results suggest the generation of an inner hydrophobic "core" due to the interaction of highly hydrophobic aromatic rings that is surface-decorated by CS groups available in a thiolato anionic form. This aggregation mechanism is supported by the fact that methoxylation of the aromatic ring dramatically strengthens the solute-solute affinity, as expressed by the sharp increase in Tm and makes these derivatives much more water-insoluble. Finally, overall findings indicate that for these compounds, solubility predictions based on lipophilicity calculations are not reliable and a more thorough characterization is required.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. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; ArgentinaFil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaRoyal Society of Chemistry2010-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112987Glisoni, Romina Julieta; Chiappetta, Diego Andrés; Finkielsztein, Liliana Mónica; Moglioni, Albertina Gladys; Sosnik, Alejandro Dario; Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity; Royal Society of Chemistry; New Journal of Chemistry; 34; 9; 6-2010; 2047-20581144-0546CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/Content/ArticleLanding/2010/NJ/C0NJ00061Binfo:eu-repo/semantics/altIdentifier/doi/10.1039/C0NJ00061Binfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:36:16Zoai:ri.conicet.gov.ar:11336/112987instacron: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 09:36:16.775CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
title Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
spellingShingle Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
Glisoni, Romina Julieta
SELF-AGGREGATION
THIOSEMICARBAZONE
ANTIVIRAL ACTIVITY
title_short Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
title_full Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
title_fullStr Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
title_full_unstemmed Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
title_sort Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity
dc.creator.none.fl_str_mv Glisoni, Romina Julieta
Chiappetta, Diego Andrés
Finkielsztein, Liliana Mónica
Moglioni, Albertina Gladys
Sosnik, Alejandro Dario
author Glisoni, Romina Julieta
author_facet Glisoni, Romina Julieta
Chiappetta, Diego Andrés
Finkielsztein, Liliana Mónica
Moglioni, Albertina Gladys
Sosnik, Alejandro Dario
author_role author
author2 Chiappetta, Diego Andrés
Finkielsztein, Liliana Mónica
Moglioni, Albertina Gladys
Sosnik, Alejandro Dario
author2_role author
author
author
author
dc.subject.none.fl_str_mv SELF-AGGREGATION
THIOSEMICARBAZONE
ANTIVIRAL ACTIVITY
topic SELF-AGGREGATION
THIOSEMICARBAZONE
ANTIVIRAL ACTIVITY
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 present work aimed to gain further insight into the mechanisms governing the aggregation process of 1-indanone thiosemicarbazone drug candidates. Regardless of the relatively low lipophilicity predicted by theoretical calculations, these compounds were very insoluble in water. This performance was especially notorious for methoxylated (and non-N-allylated) derivatives. Thermal analysis revealed that the introduction of one and two CH3O- moieties into the aromatic ring increases the Tm pronouncedly from 185 °C to 229°C and 258 °C, respectively. The formation of nano-aggregates in water was suggested by the appearance of a new strong absorption peak at 233-239 nm in the UV spectra. DLS analysis showed the early formation nanoscopic particles (120-300 nm) that undergo a gradual size growth to generate larger submicron structures; these particles remained invisible to the naked eye. The negatively-charged character of the surface was established by zeta potential measurements. These results suggest the generation of an inner hydrophobic "core" due to the interaction of highly hydrophobic aromatic rings that is surface-decorated by CS groups available in a thiolato anionic form. This aggregation mechanism is supported by the fact that methoxylation of the aromatic ring dramatically strengthens the solute-solute affinity, as expressed by the sharp increase in Tm and makes these derivatives much more water-insoluble. Finally, overall findings indicate that for these compounds, solubility predictions based on lipophilicity calculations are not reliable and a more thorough characterization is required.
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. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finkielsztein, Liliana Mónica. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Sosnik, Alejandro Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
description The present work aimed to gain further insight into the mechanisms governing the aggregation process of 1-indanone thiosemicarbazone drug candidates. Regardless of the relatively low lipophilicity predicted by theoretical calculations, these compounds were very insoluble in water. This performance was especially notorious for methoxylated (and non-N-allylated) derivatives. Thermal analysis revealed that the introduction of one and two CH3O- moieties into the aromatic ring increases the Tm pronouncedly from 185 °C to 229°C and 258 °C, respectively. The formation of nano-aggregates in water was suggested by the appearance of a new strong absorption peak at 233-239 nm in the UV spectra. DLS analysis showed the early formation nanoscopic particles (120-300 nm) that undergo a gradual size growth to generate larger submicron structures; these particles remained invisible to the naked eye. The negatively-charged character of the surface was established by zeta potential measurements. These results suggest the generation of an inner hydrophobic "core" due to the interaction of highly hydrophobic aromatic rings that is surface-decorated by CS groups available in a thiolato anionic form. This aggregation mechanism is supported by the fact that methoxylation of the aromatic ring dramatically strengthens the solute-solute affinity, as expressed by the sharp increase in Tm and makes these derivatives much more water-insoluble. Finally, overall findings indicate that for these compounds, solubility predictions based on lipophilicity calculations are not reliable and a more thorough characterization is required.
publishDate 2010
dc.date.none.fl_str_mv 2010-06
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/11336/112987
Glisoni, Romina Julieta; Chiappetta, Diego Andrés; Finkielsztein, Liliana Mónica; Moglioni, Albertina Gladys; Sosnik, Alejandro Dario; Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity; Royal Society of Chemistry; New Journal of Chemistry; 34; 9; 6-2010; 2047-2058
1144-0546
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112987
identifier_str_mv Glisoni, Romina Julieta; Chiappetta, Diego Andrés; Finkielsztein, Liliana Mónica; Moglioni, Albertina Gladys; Sosnik, Alejandro Dario; Self-aggregation behaviour of novel thiosemicarbazone drug candidates with potential antiviral activity; Royal Society of Chemistry; New Journal of Chemistry; 34; 9; 6-2010; 2047-2058
1144-0546
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://pubs.rsc.org/en/Content/ArticleLanding/2010/NJ/C0NJ00061B
info:eu-repo/semantics/altIdentifier/doi/10.1039/C0NJ00061B
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
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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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