Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents

Autores
Bruna Haupt, Ezequiel Fabricio; Perretti, Marcelle D.; Garro, Hugo A.; Carrillo, Romen; Machín, Félix; Lorenzo Castrillejo, Isabel; Gutiérrez, Lucas; Vega Hissi, Esteban Gabriel; Mamberto, Macarena; Menacho Márquez, Mauricio Ariel; Fernández, Claudio O.; García, Celina; Pungitore, Carlos Rodolfo
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.
Fil: Bruna Haupt, Ezequiel Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Perretti, Marcelle D.. Universidad de La Laguna; España
Fil: Garro, Hugo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Carrillo, Romen. Universidad de La Laguna; España
Fil: Machín, Félix. Universidad de Las Palmas de Gran Canaria; España
Fil: Lorenzo Castrillejo, Isabel. Universidad de La Laguna; España
Fil: Gutiérrez, Lucas. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina
Fil: Mamberto, Macarena. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Menacho Márquez, Mauricio Ariel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Fernández, Claudio O.. Universidad Nacional de Rosario; Argentina
Fil: García, Celina. Universidad de la Laguna. Departamento de Química Orgánica; España
Fil: Pungitore, Carlos Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Materia
Synthesis
Coumarin
Antiproliferative
Natural Products
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:11336/227406
Acceder
id CONICETDig_21edd06ad780d277b98e777913921dd1
oai_identifier_str oai:ri.conicet.gov.ar:11336/227406
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative AgentsBruna Haupt, Ezequiel FabricioPerretti, Marcelle D.Garro, Hugo A.Carrillo, RomenMachín, FélixLorenzo Castrillejo, IsabelGutiérrez, LucasVega Hissi, Esteban GabrielMamberto, MacarenaMenacho Márquez, Mauricio ArielFernández, Claudio O.García, CelinaPungitore, Carlos RodolfoSynthesisCoumarinAntiproliferativeNatural Productshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.Fil: Bruna Haupt, Ezequiel Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Perretti, Marcelle D.. Universidad de La Laguna; EspañaFil: Garro, Hugo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Carrillo, Romen. Universidad de La Laguna; EspañaFil: Machín, Félix. Universidad de Las Palmas de Gran Canaria; EspañaFil: Lorenzo Castrillejo, Isabel. Universidad de La Laguna; EspañaFil: Gutiérrez, Lucas. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; ArgentinaFil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Mamberto, Macarena. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Menacho Márquez, Mauricio Ariel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Fernández, Claudio O.. Universidad Nacional de Rosario; ArgentinaFil: García, Celina. Universidad de la Laguna. Departamento de Química Orgánica; EspañaFil: Pungitore, Carlos Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaAmerican Chemical Society2023-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227406Bruna Haupt, Ezequiel Fabricio; Perretti, Marcelle D.; Garro, Hugo A.; Carrillo, Romen; Machín, Félix; et al.; Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents; American Chemical Society; ACS Omega; 8; 29; 7-2023; 26479-264962470-13432470-1343CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsomega.3c03181info:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.3c03181info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:10:40Zoai:ri.conicet.gov.ar:11336/227406instacron: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 10:10:40.539CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
title Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
spellingShingle Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
Bruna Haupt, Ezequiel Fabricio
Synthesis
Coumarin
Antiproliferative
Natural Products
title_short Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
title_full Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
title_fullStr Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
title_full_unstemmed Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
title_sort Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents
dc.creator.none.fl_str_mv Bruna Haupt, Ezequiel Fabricio
Perretti, Marcelle D.
Garro, Hugo A.
Carrillo, Romen
Machín, Félix
Lorenzo Castrillejo, Isabel
Gutiérrez, Lucas
Vega Hissi, Esteban Gabriel
Mamberto, Macarena
Menacho Márquez, Mauricio Ariel
Fernández, Claudio O.
García, Celina
Pungitore, Carlos Rodolfo
author Bruna Haupt, Ezequiel Fabricio
author_facet Bruna Haupt, Ezequiel Fabricio
Perretti, Marcelle D.
Garro, Hugo A.
Carrillo, Romen
Machín, Félix
Lorenzo Castrillejo, Isabel
Gutiérrez, Lucas
Vega Hissi, Esteban Gabriel
Mamberto, Macarena
Menacho Márquez, Mauricio Ariel
Fernández, Claudio O.
García, Celina
Pungitore, Carlos Rodolfo
author_role author
author2 Perretti, Marcelle D.
Garro, Hugo A.
Carrillo, Romen
Machín, Félix
Lorenzo Castrillejo, Isabel
Gutiérrez, Lucas
Vega Hissi, Esteban Gabriel
Mamberto, Macarena
Menacho Márquez, Mauricio Ariel
Fernández, Claudio O.
García, Celina
Pungitore, Carlos Rodolfo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Synthesis
Coumarin
Antiproliferative
Natural Products
topic Synthesis
Coumarin
Antiproliferative
Natural Products
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 library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.
Fil: Bruna Haupt, Ezequiel Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Perretti, Marcelle D.. Universidad de La Laguna; España
Fil: Garro, Hugo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
Fil: Carrillo, Romen. Universidad de La Laguna; España
Fil: Machín, Félix. Universidad de Las Palmas de Gran Canaria; España
Fil: Lorenzo Castrillejo, Isabel. Universidad de La Laguna; España
Fil: Gutiérrez, Lucas. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina
Fil: Vega Hissi, Esteban Gabriel. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina
Fil: Mamberto, Macarena. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Menacho Márquez, Mauricio Ariel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Fernández, Claudio O.. Universidad Nacional de Rosario; Argentina
Fil: García, Celina. Universidad de la Laguna. Departamento de Química Orgánica; España
Fil: Pungitore, Carlos Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; Argentina
description A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.
publishDate 2023
dc.date.none.fl_str_mv 2023-07
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/11336/227406
Bruna Haupt, Ezequiel Fabricio; Perretti, Marcelle D.; Garro, Hugo A.; Carrillo, Romen; Machín, Félix; et al.; Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents; American Chemical Society; ACS Omega; 8; 29; 7-2023; 26479-26496
2470-1343
2470-1343
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227406
identifier_str_mv Bruna Haupt, Ezequiel Fabricio; Perretti, Marcelle D.; Garro, Hugo A.; Carrillo, Romen; Machín, Félix; et al.; Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents; American Chemical Society; ACS Omega; 8; 29; 7-2023; 26479-26496
2470-1343
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsomega.3c03181
info:eu-repo/semantics/altIdentifier/doi/10.1021/acsomega.3c03181
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_ 1844613997897187328
score 13.070432

Publicaciones similares