Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents

Autores
Abonia, Rodrigo; Garay, Alexander; Castillo, Juan C.; Insuasty, Braulio; Quiroga, Jairo; Nogueras, Manuel; Cobo, Justo; Butassi, Estefanía; Zacchino, Susana Alicia Stella
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, theγ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 μg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 μg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 μg/mL against C. neoformans.
Fil: Abonia, Rodrigo. Universidad del Valle; Colombia
Fil: Garay, Alexander. Universidad del Valle; Colombia
Fil: Castillo, Juan C.. Universidad del Valle; Colombia. Universidad Pedagógica y Tecnológica de Colombia; Colombia
Fil: Insuasty, Braulio. Universidad del Valle; Colombia
Fil: Quiroga, Jairo. Universidad del Valle; Colombia
Fil: Nogueras, Manuel. Universidad de Jaén; España
Fil: Cobo, Justo. Universidad de Jaén; España
Fil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
Materia
ALLYAMINES
ANTIFUNGAL ACTIVITY
BENZYLAMINES
MANNICH-TYPE REACTION
NAFTIFINE ANALOGUES
PROPIOPHENONE SALTS
Γ-AMINOALCOHOLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/87771
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/87771
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agentsAbonia, RodrigoGaray, AlexanderCastillo, Juan C.Insuasty, BraulioQuiroga, JairoNogueras, ManuelCobo, JustoButassi, EstefaníaZacchino, Susana Alicia StellaALLYAMINESANTIFUNGAL ACTIVITYBENZYLAMINESMANNICH-TYPE REACTIONNAFTIFINE ANALOGUESPROPIOPHENONE SALTSΓ-AMINOALCOHOLShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, theγ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 μg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 μg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 μg/mL against C. neoformans.Fil: Abonia, Rodrigo. Universidad del Valle; ColombiaFil: Garay, Alexander. Universidad del Valle; ColombiaFil: Castillo, Juan C.. Universidad del Valle; Colombia. Universidad Pedagógica y Tecnológica de Colombia; ColombiaFil: Insuasty, Braulio. Universidad del Valle; ColombiaFil: Quiroga, Jairo. Universidad del Valle; ColombiaFil: Nogueras, Manuel. Universidad de Jaén; EspañaFil: Cobo, Justo. Universidad de Jaén; EspañaFil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; ArgentinaMolecular Diversity Preservation International2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/87771Abonia, Rodrigo; Garay, Alexander; Castillo, Juan C.; Insuasty, Braulio; Quiroga, Jairo; et al.; Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents; Molecular Diversity Preservation International; Molecules; 23; 3; 2-2018; 1-221420-3049CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/3/520info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23030520info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:04Zoai:ri.conicet.gov.ar:11336/87771instacron: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 09:40:04.699CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
title Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
spellingShingle Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
Abonia, Rodrigo
ALLYAMINES
ANTIFUNGAL ACTIVITY
BENZYLAMINES
MANNICH-TYPE REACTION
NAFTIFINE ANALOGUES
PROPIOPHENONE SALTS
Γ-AMINOALCOHOLS
title_short Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
title_full Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
title_fullStr Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
title_full_unstemmed Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
title_sort Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents
dc.creator.none.fl_str_mv Abonia, Rodrigo
Garay, Alexander
Castillo, Juan C.
Insuasty, Braulio
Quiroga, Jairo
Nogueras, Manuel
Cobo, Justo
Butassi, Estefanía
Zacchino, Susana Alicia Stella
author Abonia, Rodrigo
author_facet Abonia, Rodrigo
Garay, Alexander
Castillo, Juan C.
Insuasty, Braulio
Quiroga, Jairo
Nogueras, Manuel
Cobo, Justo
Butassi, Estefanía
Zacchino, Susana Alicia Stella
author_role author
author2 Garay, Alexander
Castillo, Juan C.
Insuasty, Braulio
Quiroga, Jairo
Nogueras, Manuel
Cobo, Justo
Butassi, Estefanía
Zacchino, Susana Alicia Stella
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ALLYAMINES
ANTIFUNGAL ACTIVITY
BENZYLAMINES
MANNICH-TYPE REACTION
NAFTIFINE ANALOGUES
PROPIOPHENONE SALTS
Γ-AMINOALCOHOLS
topic ALLYAMINES
ANTIFUNGAL ACTIVITY
BENZYLAMINES
MANNICH-TYPE REACTION
NAFTIFINE ANALOGUES
PROPIOPHENONE SALTS
Γ-AMINOALCOHOLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, theγ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 μg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 μg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 μg/mL against C. neoformans.
Fil: Abonia, Rodrigo. Universidad del Valle; Colombia
Fil: Garay, Alexander. Universidad del Valle; Colombia
Fil: Castillo, Juan C.. Universidad del Valle; Colombia. Universidad Pedagógica y Tecnológica de Colombia; Colombia
Fil: Insuasty, Braulio. Universidad del Valle; Colombia
Fil: Quiroga, Jairo. Universidad del Valle; Colombia
Fil: Nogueras, Manuel. Universidad de Jaén; España
Fil: Cobo, Justo. Universidad de Jaén; España
Fil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina
description Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, theγ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 μg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 μg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 μg/mL against C. neoformans.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
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/11336/87771
Abonia, Rodrigo; Garay, Alexander; Castillo, Juan C.; Insuasty, Braulio; Quiroga, Jairo; et al.; Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents; Molecular Diversity Preservation International; Molecules; 23; 3; 2-2018; 1-22
1420-3049
CONICET Digital
CONICET
url http://hdl.handle.net/11336/87771
identifier_str_mv Abonia, Rodrigo; Garay, Alexander; Castillo, Juan C.; Insuasty, Braulio; Quiroga, Jairo; et al.; Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents; Molecular Diversity Preservation International; Molecules; 23; 3; 2-2018; 1-22
1420-3049
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.mdpi.com/1420-3049/23/3/520
info:eu-repo/semantics/altIdentifier/doi/10.3390/molecules23030520
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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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