Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents

Autores
Ramírez, Juan; Svetaz, Laura Andrea; Quiroga, Jairo; Abonia, Rodrigo; Raimondi, Marcela; Zacchino, Susana; Insuasty, Braulio
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a–g and 7a–g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a–g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28–2.98 μM and 0.35–2.78 μM respectively under in vitro assays. In addition, 6a–g and 7a–g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a–g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8–31.2 μg/mL, MIC80 = 15.6–31.2 μg/mL and MIC100 = 15.6–62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.
Fil: Ramírez, Juan. Universidad del Valle. Departamento de Química; Colombia
Fil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Quiroga, Jairo. Universidad del Valle. Departamento de Química; Colombia
Fil: Abonia, Rodrigo. Universidad del Valle. Departamento de Química; Colombia
Fil: Raimondi, Marcela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Insuasty, Braulio. Universidad del Valle. Departamento de Química; Colombia
Materia
Thiazole
Regioselectivity
Pyrimido[4,5-B][1,4]Diazepines
Antitumor Activity
Antifungal 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:11336/13358
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13358
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agentsRamírez, JuanSvetaz, Laura AndreaQuiroga, JairoAbonia, RodrigoRaimondi, MarcelaZacchino, SusanaInsuasty, BraulioThiazoleRegioselectivityPyrimido[4,5-B][1,4]DiazepinesAntitumor ActivityAntifungal Activityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a–g and 7a–g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a–g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28–2.98 μM and 0.35–2.78 μM respectively under in vitro assays. In addition, 6a–g and 7a–g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a–g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8–31.2 μg/mL, MIC80 = 15.6–31.2 μg/mL and MIC100 = 15.6–62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.Fil: Ramírez, Juan. Universidad del Valle. Departamento de Química; ColombiaFil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; ArgentinaFil: Quiroga, Jairo. Universidad del Valle. Departamento de Química; ColombiaFil: Abonia, Rodrigo. Universidad del Valle. Departamento de Química; ColombiaFil: Raimondi, Marcela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; ArgentinaFil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; ArgentinaFil: Insuasty, Braulio. Universidad del Valle. Departamento de Química; ColombiaElsevier Masson2015-03info: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/11336/13358Ramírez, Juan; Svetaz, Laura Andrea; Quiroga, Jairo; Abonia, Rodrigo; Raimondi, Marcela; et al.; Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents; Elsevier Masson; European Journal Of Medical Chemistry; 92; 3-2015; 866–8750223-5234enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2015.01.053info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523415000732info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:26:26Zoai:ri.conicet.gov.ar:11336/13358instacron: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:34982025-10-15 14:26:26.797CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
title Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
spellingShingle Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
Ramírez, Juan
Thiazole
Regioselectivity
Pyrimido[4,5-B][1,4]Diazepines
Antitumor Activity
Antifungal Activity
title_short Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
title_full Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
title_fullStr Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
title_full_unstemmed Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
title_sort Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents
dc.creator.none.fl_str_mv Ramírez, Juan
Svetaz, Laura Andrea
Quiroga, Jairo
Abonia, Rodrigo
Raimondi, Marcela
Zacchino, Susana
Insuasty, Braulio
author Ramírez, Juan
author_facet Ramírez, Juan
Svetaz, Laura Andrea
Quiroga, Jairo
Abonia, Rodrigo
Raimondi, Marcela
Zacchino, Susana
Insuasty, Braulio
author_role author
author2 Svetaz, Laura Andrea
Quiroga, Jairo
Abonia, Rodrigo
Raimondi, Marcela
Zacchino, Susana
Insuasty, Braulio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Thiazole
Regioselectivity
Pyrimido[4,5-B][1,4]Diazepines
Antitumor Activity
Antifungal Activity
topic Thiazole
Regioselectivity
Pyrimido[4,5-B][1,4]Diazepines
Antitumor Activity
Antifungal 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 new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a–g and 7a–g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a–g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28–2.98 μM and 0.35–2.78 μM respectively under in vitro assays. In addition, 6a–g and 7a–g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a–g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8–31.2 μg/mL, MIC80 = 15.6–31.2 μg/mL and MIC100 = 15.6–62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.
Fil: Ramírez, Juan. Universidad del Valle. Departamento de Química; Colombia
Fil: Svetaz, Laura Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Quiroga, Jairo. Universidad del Valle. Departamento de Química; Colombia
Fil: Abonia, Rodrigo. Universidad del Valle. Departamento de Química; Colombia
Fil: Raimondi, Marcela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Zacchino, Susana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Area Farmacognosia; Argentina
Fil: Insuasty, Braulio. Universidad del Valle. Departamento de Química; Colombia
description A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a–g and 7a–g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,β-unsaturated carbonyl compounds 3a–g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28–2.98 μM and 0.35–2.78 μM respectively under in vitro assays. In addition, 6a–g and 7a–g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a–g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8–31.2 μg/mL, MIC80 = 15.6–31.2 μg/mL and MIC100 = 15.6–62.5 μg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
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/11336/13358
Ramírez, Juan; Svetaz, Laura Andrea; Quiroga, Jairo; Abonia, Rodrigo; Raimondi, Marcela; et al.; Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents; Elsevier Masson; European Journal Of Medical Chemistry; 92; 3-2015; 866–875
0223-5234
url http://hdl.handle.net/11336/13358
identifier_str_mv Ramírez, Juan; Svetaz, Laura Andrea; Quiroga, Jairo; Abonia, Rodrigo; Raimondi, Marcela; et al.; Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents; Elsevier Masson; European Journal Of Medical Chemistry; 92; 3-2015; 866–875
0223-5234
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.2015.01.053
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0223523415000732
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_ 1846082709547384832
score 12.891075

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