Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations...

Autores
Martini, María Florencia; Glisoni, Romina Julieta; Sosnik, Alejandro Dario; Moglioni, Albertina Gladys; Pickholz, Mónica Andrea
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
1-Indanone thiosemicarbazones (TSCs) display a broad spectrum of pharmacological activities. However, their extremely poor solubility and self-aggregation tendency in water hurdles the reliable evaluation of the activity in vitro. To overcome these drawbacks, the formation of complexes with different natural and chemically modified cyclodextrins (CDs) has been investigated. Aiming to gain further insight into the molecular mechanisms involved in the interaction of these new chemical entities with CDs, this work investigated for the first time the interaction of two types of 1-indanone TSCs with hydroxyl-propyl-β-CD (HPβ-CD) by Molecular Dynamics (MD) simulations. Results were in good agreement with the experimental work and revealed the fundamental contribution of the substituents in the 1-indanone aromatic ring not only to the intrinsic aqueous solubility but also more importantly to the self-aggregation and the ability of the TSC to form stable complexes with the CD. In the particular case of the 5,6-dimethoxy-1-indanone derivative, the increase of the solubility in presence of HPβ-CD stems from a considerable decrease of the TSC-TSC intermolecular interactions and the formation of inclusion complexes that are stable for a short time. Then, the high self-aggregation tendency of this TSC destabilizes the complex and leads to the initial TSC insolubilization and subsequent precipitation.
Fil: Martini, María Florencia. 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
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Fil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; Israel
Fil: Moglioni, Albertina Gladys. 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
Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Materia
Complex Formation
Cyclodextrins
Molecular Dynamics
Thiosemicarbazones of 1-Indanone
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:11336/40447
Acceder
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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulationsMartini, María FlorenciaGlisoni, Romina JulietaSosnik, Alejandro DarioMoglioni, Albertina GladysPickholz, Mónica AndreaComplex FormationCyclodextrinsMolecular DynamicsThiosemicarbazones of 1-Indanonehttps://purl.org/becyt/ford/2.10https://purl.org/becyt/ford/21-Indanone thiosemicarbazones (TSCs) display a broad spectrum of pharmacological activities. However, their extremely poor solubility and self-aggregation tendency in water hurdles the reliable evaluation of the activity in vitro. To overcome these drawbacks, the formation of complexes with different natural and chemically modified cyclodextrins (CDs) has been investigated. Aiming to gain further insight into the molecular mechanisms involved in the interaction of these new chemical entities with CDs, this work investigated for the first time the interaction of two types of 1-indanone TSCs with hydroxyl-propyl-β-CD (HPβ-CD) by Molecular Dynamics (MD) simulations. Results were in good agreement with the experimental work and revealed the fundamental contribution of the substituents in the 1-indanone aromatic ring not only to the intrinsic aqueous solubility but also more importantly to the self-aggregation and the ability of the TSC to form stable complexes with the CD. In the particular case of the 5,6-dimethoxy-1-indanone derivative, the increase of the solubility in presence of HPβ-CD stems from a considerable decrease of the TSC-TSC intermolecular interactions and the formation of inclusion complexes that are stable for a short time. Then, the high self-aggregation tendency of this TSC destabilizes the complex and leads to the initial TSC insolubilization and subsequent precipitation.Fil: Martini, María Florencia. 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; ArgentinaFil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; IsraelFil: Moglioni, Albertina Gladys. 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; ArgentinaFil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaElsevier Science2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/40447Martini, María Florencia; Glisoni, Romina Julieta; Sosnik, Alejandro Dario; Moglioni, Albertina Gladys; Pickholz, Mónica Andrea; Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations; Elsevier Science; Journal of Molecular Liquids; 222; 10-2016; 963-9710167-7322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.molliq.2016.07.109info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0167732216303038info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:33:41Zoai:ri.conicet.gov.ar:11336/40447instacron: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 09:33:42.177CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
title Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
spellingShingle Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
Martini, María Florencia
Complex Formation
Cyclodextrins
Molecular Dynamics
Thiosemicarbazones of 1-Indanone
title_short Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
title_full Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
title_fullStr Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
title_full_unstemmed Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
title_sort Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations
dc.creator.none.fl_str_mv Martini, María Florencia
Glisoni, Romina Julieta
Sosnik, Alejandro Dario
Moglioni, Albertina Gladys
Pickholz, Mónica Andrea
author Martini, María Florencia
author_facet Martini, María Florencia
Glisoni, Romina Julieta
Sosnik, Alejandro Dario
Moglioni, Albertina Gladys
Pickholz, Mónica Andrea
author_role author
author2 Glisoni, Romina Julieta
Sosnik, Alejandro Dario
Moglioni, Albertina Gladys
Pickholz, Mónica Andrea
author2_role author
author
author
author
dc.subject.none.fl_str_mv Complex Formation
Cyclodextrins
Molecular Dynamics
Thiosemicarbazones of 1-Indanone
topic Complex Formation
Cyclodextrins
Molecular Dynamics
Thiosemicarbazones of 1-Indanone
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv 1-Indanone thiosemicarbazones (TSCs) display a broad spectrum of pharmacological activities. However, their extremely poor solubility and self-aggregation tendency in water hurdles the reliable evaluation of the activity in vitro. To overcome these drawbacks, the formation of complexes with different natural and chemically modified cyclodextrins (CDs) has been investigated. Aiming to gain further insight into the molecular mechanisms involved in the interaction of these new chemical entities with CDs, this work investigated for the first time the interaction of two types of 1-indanone TSCs with hydroxyl-propyl-β-CD (HPβ-CD) by Molecular Dynamics (MD) simulations. Results were in good agreement with the experimental work and revealed the fundamental contribution of the substituents in the 1-indanone aromatic ring not only to the intrinsic aqueous solubility but also more importantly to the self-aggregation and the ability of the TSC to form stable complexes with the CD. In the particular case of the 5,6-dimethoxy-1-indanone derivative, the increase of the solubility in presence of HPβ-CD stems from a considerable decrease of the TSC-TSC intermolecular interactions and the formation of inclusion complexes that are stable for a short time. Then, the high self-aggregation tendency of this TSC destabilizes the complex and leads to the initial TSC insolubilization and subsequent precipitation.
Fil: Martini, María Florencia. 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
Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
Fil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; Israel
Fil: Moglioni, Albertina Gladys. 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
Fil: Pickholz, Mónica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; Argentina
description 1-Indanone thiosemicarbazones (TSCs) display a broad spectrum of pharmacological activities. However, their extremely poor solubility and self-aggregation tendency in water hurdles the reliable evaluation of the activity in vitro. To overcome these drawbacks, the formation of complexes with different natural and chemically modified cyclodextrins (CDs) has been investigated. Aiming to gain further insight into the molecular mechanisms involved in the interaction of these new chemical entities with CDs, this work investigated for the first time the interaction of two types of 1-indanone TSCs with hydroxyl-propyl-β-CD (HPβ-CD) by Molecular Dynamics (MD) simulations. Results were in good agreement with the experimental work and revealed the fundamental contribution of the substituents in the 1-indanone aromatic ring not only to the intrinsic aqueous solubility but also more importantly to the self-aggregation and the ability of the TSC to form stable complexes with the CD. In the particular case of the 5,6-dimethoxy-1-indanone derivative, the increase of the solubility in presence of HPβ-CD stems from a considerable decrease of the TSC-TSC intermolecular interactions and the formation of inclusion complexes that are stable for a short time. Then, the high self-aggregation tendency of this TSC destabilizes the complex and leads to the initial TSC insolubilization and subsequent precipitation.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
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/11336/40447
Martini, María Florencia; Glisoni, Romina Julieta; Sosnik, Alejandro Dario; Moglioni, Albertina Gladys; Pickholz, Mónica Andrea; Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations; Elsevier Science; Journal of Molecular Liquids; 222; 10-2016; 963-971
0167-7322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/40447
identifier_str_mv Martini, María Florencia; Glisoni, Romina Julieta; Sosnik, Alejandro Dario; Moglioni, Albertina Gladys; Pickholz, Mónica Andrea; Insights on self-aggregation phenomena of 1-indanone thiosemicarbazones and the formation of inclusion complexes with hydroxypropyl-β-cyclodextrin by Molecular Dynamics simulations; Elsevier Science; Journal of Molecular Liquids; 222; 10-2016; 963-971
0167-7322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.molliq.2016.07.109
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0167732216303038
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
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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score 13.070432

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