Antiparasitic hybrids of Cinchona alkaloids and bile acids

Autores
Leverrier, Aurélie; Bero, Joanne; Frédérich, Michel; Quetin Leclercq, Joelle; Palermo, Jorge Alejandro
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A series of 16 hybrids of Cinchona alkaloids and bile acids (4a–h, 5a–h) was prepared by means of a Barton–Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6–15.7.
Fil: Leverrier, Aurélie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Fil: Bero, Joanne. Universite Catholique de Louvain; Bélgica
Fil: Frédérich, Michel. Universite de Liege; Bélgica
Fil: Quetin Leclercq, Joelle. Universite Catholique de Louvain; Bélgica
Fil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Materia
Cinchona Alkaloids
Bile Acids
Barton-Zard Reaction
Antiparasitic 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:11336/18703
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18703
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiparasitic hybrids of Cinchona alkaloids and bile acidsLeverrier, AurélieBero, JoanneFrédérich, MichelQuetin Leclercq, JoellePalermo, Jorge AlejandroCinchona AlkaloidsBile AcidsBarton-Zard ReactionAntiparasitic Activityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A series of 16 hybrids of Cinchona alkaloids and bile acids (4a–h, 5a–h) was prepared by means of a Barton–Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6–15.7.Fil: Leverrier, Aurélie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Bero, Joanne. Universite Catholique de Louvain; BélgicaFil: Frédérich, Michel. Universite de Liege; BélgicaFil: Quetin Leclercq, Joelle. Universite Catholique de Louvain; BélgicaFil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaElsevier Masson2013-08info: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/11336/18703Leverrier, Aurélie; Bero, Joanne; Frédérich, Michel; Quetin Leclercq, Joelle; Palermo, Jorge Alejandro; Antiparasitic hybrids of Cinchona alkaloids and bile acids; Elsevier Masson; European Journal of Medical Chemistry; 66; 8-2013; 355-3630223-5234CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2013.06.004info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413003693info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:10:36Zoai:ri.conicet.gov.ar:11336/18703instacron: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:34982025-10-22 12:10:36.73CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiparasitic hybrids of Cinchona alkaloids and bile acids
title Antiparasitic hybrids of Cinchona alkaloids and bile acids
spellingShingle Antiparasitic hybrids of Cinchona alkaloids and bile acids
Leverrier, Aurélie
Cinchona Alkaloids
Bile Acids
Barton-Zard Reaction
Antiparasitic Activity
title_short Antiparasitic hybrids of Cinchona alkaloids and bile acids
title_full Antiparasitic hybrids of Cinchona alkaloids and bile acids
title_fullStr Antiparasitic hybrids of Cinchona alkaloids and bile acids
title_full_unstemmed Antiparasitic hybrids of Cinchona alkaloids and bile acids
title_sort Antiparasitic hybrids of Cinchona alkaloids and bile acids
dc.creator.none.fl_str_mv Leverrier, Aurélie
Bero, Joanne
Frédérich, Michel
Quetin Leclercq, Joelle
Palermo, Jorge Alejandro
author Leverrier, Aurélie
author_facet Leverrier, Aurélie
Bero, Joanne
Frédérich, Michel
Quetin Leclercq, Joelle
Palermo, Jorge Alejandro
author_role author
author2 Bero, Joanne
Frédérich, Michel
Quetin Leclercq, Joelle
Palermo, Jorge Alejandro
author2_role author
author
author
author
dc.subject.none.fl_str_mv Cinchona Alkaloids
Bile Acids
Barton-Zard Reaction
Antiparasitic Activity
topic Cinchona Alkaloids
Bile Acids
Barton-Zard Reaction
Antiparasitic Activity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A series of 16 hybrids of Cinchona alkaloids and bile acids (4a–h, 5a–h) was prepared by means of a Barton–Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6–15.7.
Fil: Leverrier, Aurélie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Fil: Bero, Joanne. Universite Catholique de Louvain; Bélgica
Fil: Frédérich, Michel. Universite de Liege; Bélgica
Fil: Quetin Leclercq, Joelle. Universite Catholique de Louvain; Bélgica
Fil: Palermo, Jorge Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
description A series of 16 hybrids of Cinchona alkaloids and bile acids (4a–h, 5a–h) was prepared by means of a Barton–Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6–15.7.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
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/11336/18703
Leverrier, Aurélie; Bero, Joanne; Frédérich, Michel; Quetin Leclercq, Joelle; Palermo, Jorge Alejandro; Antiparasitic hybrids of Cinchona alkaloids and bile acids; Elsevier Masson; European Journal of Medical Chemistry; 66; 8-2013; 355-363
0223-5234
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18703
identifier_str_mv Leverrier, Aurélie; Bero, Joanne; Frédérich, Michel; Quetin Leclercq, Joelle; Palermo, Jorge Alejandro; Antiparasitic hybrids of Cinchona alkaloids and bile acids; Elsevier Masson; European Journal of Medical Chemistry; 66; 8-2013; 355-363
0223-5234
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.ejmech.2013.06.004
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523413003693
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
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
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_ 1846782492342747136
score 12.982451

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