Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action

Autores
Martínez, Valeria; María V. Aguirre; Todaro, Juan Santiago; Ferrer, Evelina Gloria; Williams, Patricia Ana María
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)2(H2O)2]·2H2O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC50 75 μM) of telmisartan (IC50 125 μM) or ZnSO4 (IC50 225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased aswell as caspase-3 activation. Both the complex and the ligand bind to bovine serumalbumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van derWaals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC50 75 μM and 125 μM, respectively) and the interaction with BSA.
Fil: Martínez, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: María V. Aguirre. Universidad Nacional del Nordeste; Argentina
Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste; Argentina
Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Materia
Telmisartan
Zn(II) metal complex
Cancer
Bovine serum albumin
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:11336/127631
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/127631
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of ActionMartínez, ValeriaMaría V. AguirreTodaro, Juan SantiagoFerrer, Evelina GloriaWilliams, Patricia Ana MaríaTelmisartanZn(II) metal complexCancerBovine serum albuminhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)2(H2O)2]·2H2O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC50 75 μM) of telmisartan (IC50 125 μM) or ZnSO4 (IC50 225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased aswell as caspase-3 activation. Both the complex and the ligand bind to bovine serumalbumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van derWaals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC50 75 μM and 125 μM, respectively) and the interaction with BSA.Fil: Martínez, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: María V. Aguirre. Universidad Nacional del Nordeste; ArgentinaFil: Todaro, Juan Santiago. Universidad Nacional del Nordeste; ArgentinaFil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaHumana Press2019-12info: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/11336/127631Martínez, Valeria; María V. Aguirre; Todaro, Juan Santiago; Ferrer, Evelina Gloria; Williams, Patricia Ana María; Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action; Humana Press; Biological Trace Element Research; 197; 12-2019; 454–4630163-4984CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s12011-019-02013-winfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12011-019-02013-winfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:02:10Zoai:ri.conicet.gov.ar:11336/127631instacron: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 11:02:10.76CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
title Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
spellingShingle Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
Martínez, Valeria
Telmisartan
Zn(II) metal complex
Cancer
Bovine serum albumin
title_short Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
title_full Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
title_fullStr Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
title_full_unstemmed Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
title_sort Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action
dc.creator.none.fl_str_mv Martínez, Valeria
María V. Aguirre
Todaro, Juan Santiago
Ferrer, Evelina Gloria
Williams, Patricia Ana María
author Martínez, Valeria
author_facet Martínez, Valeria
María V. Aguirre
Todaro, Juan Santiago
Ferrer, Evelina Gloria
Williams, Patricia Ana María
author_role author
author2 María V. Aguirre
Todaro, Juan Santiago
Ferrer, Evelina Gloria
Williams, Patricia Ana María
author2_role author
author
author
author
dc.subject.none.fl_str_mv Telmisartan
Zn(II) metal complex
Cancer
Bovine serum albumin
topic Telmisartan
Zn(II) metal complex
Cancer
Bovine serum albumin
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)2(H2O)2]·2H2O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC50 75 μM) of telmisartan (IC50 125 μM) or ZnSO4 (IC50 225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased aswell as caspase-3 activation. Both the complex and the ligand bind to bovine serumalbumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van derWaals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC50 75 μM and 125 μM, respectively) and the interaction with BSA.
Fil: Martínez, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: María V. Aguirre. Universidad Nacional del Nordeste; Argentina
Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste; Argentina
Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina
description To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)2(H2O)2]·2H2O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC50 75 μM) of telmisartan (IC50 125 μM) or ZnSO4 (IC50 225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased aswell as caspase-3 activation. Both the complex and the ligand bind to bovine serumalbumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van derWaals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC50 75 μM and 125 μM, respectively) and the interaction with BSA.
publishDate 2019
dc.date.none.fl_str_mv 2019-12
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/11336/127631
Martínez, Valeria; María V. Aguirre; Todaro, Juan Santiago; Ferrer, Evelina Gloria; Williams, Patricia Ana María; Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action; Humana Press; Biological Trace Element Research; 197; 12-2019; 454–463
0163-4984
CONICET Digital
CONICET
url http://hdl.handle.net/11336/127631
identifier_str_mv Martínez, Valeria; María V. Aguirre; Todaro, Juan Santiago; Ferrer, Evelina Gloria; Williams, Patricia Ana María; Improvement of the Anticancer Activities of Telmisartan by Zn(II) Complexation and Mechanisms of Action; Humana Press; Biological Trace Element Research; 197; 12-2019; 454–463
0163-4984
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s12011-019-02013-w
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12011-019-02013-w
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 Humana Press
publisher.none.fl_str_mv Humana Press
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_ 1846781222883164160
score 12.982451

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