Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy
- Autores
- Couto, Marcos; Alamón, Catalina; García, María; Kovacs, Mariángeles; Trias, Emiliano; Nievas, Susana Isabel; Pozzi, Emiliano César Cayetano; Curotto, Paula; Thorp, Silvia Inés; Dagrosa, María Alejandra; Teixidor, Francesc; Viñas, Clara; Cerecetto, Hugo
- Año de publicación
- 2020
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy.
Fil: Couto, Marcos. Universidad de la República; Uruguay
Fil: Alamón, Catalina. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: García, María. Universidad de la República. Facultad de Ciencias; Uruguay
Fil: Kovacs, Mariángeles. Instituto Pasteur; Francia
Fil: Trias, Emiliano. Instituto Pasteur; Francia
Fil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; Argentina
Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina
Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina
Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina
Fil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Teixidor, Francesc. Consejo Superior de Investigaciones Científicas; España
Fil: Viñas, Clara. Consejo Superior de Investigaciones Científicas; España
Fil: Cerecetto, Hugo. Universidad de la República. Facultad de Química. Departamento de Química Orgánica; Uruguay - Materia
-
BORON CLUSTERS
IN VITRO BNCT EFFECT
LAPATINIB
TYROSINE KINASE INHIBITORS
[1,2,3]TRIAZOLYL LINKER - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/169051
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/169051 |
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3498 |
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CONICET Digital (CONICET) |
spelling |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture TherapyCouto, MarcosAlamón, CatalinaGarcía, MaríaKovacs, MariángelesTrias, EmilianoNievas, Susana IsabelPozzi, Emiliano César CayetanoCurotto, PaulaThorp, Silvia InésDagrosa, María AlejandraTeixidor, FrancescViñas, ClaraCerecetto, HugoBORON CLUSTERSIN VITRO BNCT EFFECTLAPATINIBTYROSINE KINASE INHIBITORS[1,2,3]TRIAZOLYL LINKERhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy.Fil: Couto, Marcos. Universidad de la República; UruguayFil: Alamón, Catalina. Universidad de la República. Facultad de Ciencias; UruguayFil: García, María. Universidad de la República. Facultad de Ciencias; UruguayFil: Kovacs, Mariángeles. Instituto Pasteur; FranciaFil: Trias, Emiliano. Instituto Pasteur; FranciaFil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; ArgentinaFil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; ArgentinaFil: Curotto, Paula. Comisión Nacional de Energía Atómica; ArgentinaFil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; ArgentinaFil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Teixidor, Francesc. Consejo Superior de Investigaciones Científicas; EspañaFil: Viñas, Clara. Consejo Superior de Investigaciones Científicas; EspañaFil: Cerecetto, Hugo. Universidad de la República. Facultad de Química. Departamento de Química Orgánica; UruguayMPDI2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169051Couto, Marcos; Alamón, Catalina; García, María; Kovacs, Mariángeles; Trias, Emiliano; et al.; Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy; MPDI; Cells; 9; 6; 6-2020; 1-182073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/9/6/1408info:eu-repo/semantics/altIdentifier/doi/10.3390/cells9061408info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:38:53Zoai:ri.conicet.gov.ar:11336/169051instacron: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 10:38:53.484CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
title |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
spellingShingle |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy Couto, Marcos BORON CLUSTERS IN VITRO BNCT EFFECT LAPATINIB TYROSINE KINASE INHIBITORS [1,2,3]TRIAZOLYL LINKER |
title_short |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
title_full |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
title_fullStr |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
title_full_unstemmed |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
title_sort |
Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy |
dc.creator.none.fl_str_mv |
Couto, Marcos Alamón, Catalina García, María Kovacs, Mariángeles Trias, Emiliano Nievas, Susana Isabel Pozzi, Emiliano César Cayetano Curotto, Paula Thorp, Silvia Inés Dagrosa, María Alejandra Teixidor, Francesc Viñas, Clara Cerecetto, Hugo |
author |
Couto, Marcos |
author_facet |
Couto, Marcos Alamón, Catalina García, María Kovacs, Mariángeles Trias, Emiliano Nievas, Susana Isabel Pozzi, Emiliano César Cayetano Curotto, Paula Thorp, Silvia Inés Dagrosa, María Alejandra Teixidor, Francesc Viñas, Clara Cerecetto, Hugo |
author_role |
author |
author2 |
Alamón, Catalina García, María Kovacs, Mariángeles Trias, Emiliano Nievas, Susana Isabel Pozzi, Emiliano César Cayetano Curotto, Paula Thorp, Silvia Inés Dagrosa, María Alejandra Teixidor, Francesc Viñas, Clara Cerecetto, Hugo |
author2_role |
author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
BORON CLUSTERS IN VITRO BNCT EFFECT LAPATINIB TYROSINE KINASE INHIBITORS [1,2,3]TRIAZOLYL LINKER |
topic |
BORON CLUSTERS IN VITRO BNCT EFFECT LAPATINIB TYROSINE KINASE INHIBITORS [1,2,3]TRIAZOLYL LINKER |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy. Fil: Couto, Marcos. Universidad de la República; Uruguay Fil: Alamón, Catalina. Universidad de la República. Facultad de Ciencias; Uruguay Fil: García, María. Universidad de la República. Facultad de Ciencias; Uruguay Fil: Kovacs, Mariángeles. Instituto Pasteur; Francia Fil: Trias, Emiliano. Instituto Pasteur; Francia Fil: Nievas, Susana Isabel. Comisión Nacional de Energía Atómica; Argentina Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica; Argentina Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina Fil: Dagrosa, María Alejandra. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Teixidor, Francesc. Consejo Superior de Investigaciones Científicas; España Fil: Viñas, Clara. Consejo Superior de Investigaciones Científicas; España Fil: Cerecetto, Hugo. Universidad de la República. Facultad de Química. Departamento de Química Orgánica; Uruguay |
description |
One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-06 |
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/11336/169051 Couto, Marcos; Alamón, Catalina; García, María; Kovacs, Mariángeles; Trias, Emiliano; et al.; Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy; MPDI; Cells; 9; 6; 6-2020; 1-18 2073-4409 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/169051 |
identifier_str_mv |
Couto, Marcos; Alamón, Catalina; García, María; Kovacs, Mariángeles; Trias, Emiliano; et al.; Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy; MPDI; Cells; 9; 6; 6-2020; 1-18 2073-4409 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://www.mdpi.com/2073-4409/9/6/1408 info:eu-repo/semantics/altIdentifier/doi/10.3390/cells9061408 |
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 |
MPDI |
publisher.none.fl_str_mv |
MPDI |
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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1844614412764184576 |
score |
13.070432 |