Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures

Autores
Suñol, Cristina; Garcia, Daniel Asmed; Bujons, Jordi; Kristofikova, Zdena; Matyas, Libor; Babot, Zoila; Kasal, Alexander
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A GABAA receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3α-hydroxy-7-nor-5α-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3α-hydroxy-7-nor-5ξ-pregnan-20-ones (5 and 6) were found to stimulate [3H]flunitrazepam binding and GABA-induced 36Cl - influx. These effects were inhibited by GABAA receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABAA receptor. © 2006 American Chemical Society.
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Superior de Investigaciones Científicas; España
Fil: Bujons, Jordi. Consejo Superior de Investigaciones Científicas; España
Fil: Kristofikova, Zdena. Academy of Sciences of the Czech Republic; República Checa
Fil: Matyas, Libor. Academy of Sciences of the Czech Republic; República Checa
Fil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; España
Fil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República Checa
Materia
Neurosteroids
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
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:11336/55491
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/55491
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal culturesSuñol, CristinaGarcia, Daniel AsmedBujons, JordiKristofikova, ZdenaMatyas, LiborBabot, ZoilaKasal, AlexanderNeurosteroidsGabaa ReceptorPharmacophore ModelReceptor Binding And Chloride Fluxhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A GABAA receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3α-hydroxy-7-nor-5α-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3α-hydroxy-7-nor-5ξ-pregnan-20-ones (5 and 6) were found to stimulate [3H]flunitrazepam binding and GABA-induced 36Cl - influx. These effects were inhibited by GABAA receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABAA receptor. © 2006 American Chemical Society.Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; EspañaFil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Superior de Investigaciones Científicas; EspañaFil: Bujons, Jordi. Consejo Superior de Investigaciones Científicas; EspañaFil: Kristofikova, Zdena. Academy of Sciences of the Czech Republic; República ChecaFil: Matyas, Libor. Academy of Sciences of the Czech Republic; República ChecaFil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; EspañaFil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República ChecaAmerican Chemical Society2006-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55491Suñol, Cristina; Garcia, Daniel Asmed; Bujons, Jordi; Kristofikova, Zdena; Matyas, Libor; et al.; Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures; American Chemical Society; Journal of Medicinal Chemistry; 49; 11; 6-2006; 3225-32340022-2623CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/jm060002finfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/jm060002finfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:54Zoai:ri.conicet.gov.ar:11336/55491instacron: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 09:50:54.632CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
title Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
spellingShingle Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
Suñol, Cristina
Neurosteroids
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
title_short Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
title_full Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
title_fullStr Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
title_full_unstemmed Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
title_sort Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures
dc.creator.none.fl_str_mv Suñol, Cristina
Garcia, Daniel Asmed
Bujons, Jordi
Kristofikova, Zdena
Matyas, Libor
Babot, Zoila
Kasal, Alexander
author Suñol, Cristina
author_facet Suñol, Cristina
Garcia, Daniel Asmed
Bujons, Jordi
Kristofikova, Zdena
Matyas, Libor
Babot, Zoila
Kasal, Alexander
author_role author
author2 Garcia, Daniel Asmed
Bujons, Jordi
Kristofikova, Zdena
Matyas, Libor
Babot, Zoila
Kasal, Alexander
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurosteroids
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
topic Neurosteroids
Gabaa Receptor
Pharmacophore Model
Receptor Binding And Chloride Flux
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 GABAA receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3α-hydroxy-7-nor-5α-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3α-hydroxy-7-nor-5ξ-pregnan-20-ones (5 and 6) were found to stimulate [3H]flunitrazepam binding and GABA-induced 36Cl - influx. These effects were inhibited by GABAA receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABAA receptor. © 2006 American Chemical Society.
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
Fil: Garcia, Daniel Asmed. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Superior de Investigaciones Científicas; España
Fil: Bujons, Jordi. Consejo Superior de Investigaciones Científicas; España
Fil: Kristofikova, Zdena. Academy of Sciences of the Czech Republic; República Checa
Fil: Matyas, Libor. Academy of Sciences of the Czech Republic; República Checa
Fil: Babot, Zoila. Consejo Superior de Investigaciones Científicas; España
Fil: Kasal, Alexander. Academy of Sciences of the Czech Republic; República Checa
description A GABAA receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3α-hydroxy-7-nor-5α-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3α-hydroxy-7-nor-5ξ-pregnan-20-ones (5 and 6) were found to stimulate [3H]flunitrazepam binding and GABA-induced 36Cl - influx. These effects were inhibited by GABAA receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABAA receptor. © 2006 American Chemical Society.
publishDate 2006
dc.date.none.fl_str_mv 2006-06
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/11336/55491
Suñol, Cristina; Garcia, Daniel Asmed; Bujons, Jordi; Kristofikova, Zdena; Matyas, Libor; et al.; Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures; American Chemical Society; Journal of Medicinal Chemistry; 49; 11; 6-2006; 3225-3234
0022-2623
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55491
identifier_str_mv Suñol, Cristina; Garcia, Daniel Asmed; Bujons, Jordi; Kristofikova, Zdena; Matyas, Libor; et al.; Activity of B-nor analogues of neurosteroids on the GABAA receptor in primary neuronal cultures; American Chemical Society; Journal of Medicinal Chemistry; 49; 11; 6-2006; 3225-3234
0022-2623
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/jm060002f
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/jm060002f
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 American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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
_version_ 1844613567926501376
score 13.070432

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