Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential

The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive abili...

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Autores: Leal, Jorge, Santos Peinado, Lucía, Fernández-Aroca, Diego M., Cuevas-Vicario, José Vicente, Martínez Lorente, Mª Ángeles, Massaguer i Vall-llovera, Anna, Jalón, Félix A., Ruiz-Hidalgo, María José, Sánchez-Prieto, Ricardo, Rodríguez, Ana María Blanco, Castañeda Peñalvo, Gregorio, Durá, Gema, Carriõn, María Carmen, Barrabés Vera, Sílvia, Manzano, Blanca R.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/26257
Acceso en línea:http://hdl.handle.net/10256/26257
Access Level:acceso abierto
Palabra clave:Càncer
Quimioteràpia del càncer
Cancer
Cancer chemotherapy
Patí -- Ús terapèutic
Platinum -- Therapeutic use
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spelling Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potentialLeal, JorgeSantos Peinado, LucíaFernández-Aroca, Diego M.Cuevas-Vicario, José VicenteMartínez Lorente, Mª ÁngelesMassaguer i Vall-llovera, AnnaJalón, Félix A.Ruiz-Hidalgo, María JoséSánchez-Prieto, RicardoRodríguez, Ana María BlancoCastañeda Peñalvo, GregorioDurá, GemaCarriõn, María CarmenBarrabés Vera, SílviaManzano, Blanca R.CàncerQuimioteràpia del càncerCancerCancer chemotherapyPatí -- Ús terapèuticPlatinum -- Therapeutic useThe problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was foundElsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/26257© Journal of Inorganic Biochemistry, 2021, vol. 218, art.núm.111403Articles publicats (D-B)Leal, Jorge Santos, Lúcia H.M.L.M. Fernández-Aroca, Diego M. Cuevas-Vicario, José Vicente Martínez, Ma Ángeles Massaguer i Vall-llovera, Anna Jalón, Félix A. Ruiz-Hidalgo, María José Sánchez-Prieto, Ricardo Rodríguez, Ana maría Blanco Castañeda Peñalvo, Gregorio Dura, Gema Carriõn, María Carmen Barrabés Vera, Sílvia Manzano, Blanca R. 2021 Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential. Journal of Inorganic Biochemistry 218 art.núm.111403reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jinorgbio.2021.111403info:eu-repo/semantics/altIdentifier/issn/0162-0134info:eu-repo/semantics/altIdentifier/eissn/1873-3344Reconeixement-NoComercial-SenseObraDerivada 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10256/262572026-05-29T05:05:01Z
dc.title.none.fl_str_mv Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
title Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
spellingShingle Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
Leal, Jorge
Càncer
Quimioteràpia del càncer
Cancer
Cancer chemotherapy
Patí -- Ús terapèutic
Platinum -- Therapeutic use
title_short Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
title_full Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
title_fullStr Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
title_full_unstemmed Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
title_sort Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential
dc.creator.none.fl_str_mv Leal, Jorge
Santos Peinado, Lucía
Fernández-Aroca, Diego M.
Cuevas-Vicario, José Vicente
Martínez Lorente, Mª Ángeles
Massaguer i Vall-llovera, Anna
Jalón, Félix A.
Ruiz-Hidalgo, María José
Sánchez-Prieto, Ricardo
Rodríguez, Ana María Blanco
Castañeda Peñalvo, Gregorio
Durá, Gema
Carriõn, María Carmen
Barrabés Vera, Sílvia
Manzano, Blanca R.
author Leal, Jorge
author_facet Leal, Jorge
Santos Peinado, Lucía
Fernández-Aroca, Diego M.
Cuevas-Vicario, José Vicente
Martínez Lorente, Mª Ángeles
Massaguer i Vall-llovera, Anna
Jalón, Félix A.
Ruiz-Hidalgo, María José
Sánchez-Prieto, Ricardo
Rodríguez, Ana María Blanco
Castañeda Peñalvo, Gregorio
Durá, Gema
Carriõn, María Carmen
Barrabés Vera, Sílvia
Manzano, Blanca R.
author_role author
author2 Santos Peinado, Lucía
Fernández-Aroca, Diego M.
Cuevas-Vicario, José Vicente
Martínez Lorente, Mª Ángeles
Massaguer i Vall-llovera, Anna
Jalón, Félix A.
Ruiz-Hidalgo, María José
Sánchez-Prieto, Ricardo
Rodríguez, Ana María Blanco
Castañeda Peñalvo, Gregorio
Durá, Gema
Carriõn, María Carmen
Barrabés Vera, Sílvia
Manzano, Blanca R.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer
Quimioteràpia del càncer
Cancer
Cancer chemotherapy
Patí -- Ús terapèutic
Platinum -- Therapeutic use
topic Càncer
Quimioteràpia del càncer
Cancer
Cancer chemotherapy
Patí -- Ús terapèutic
Platinum -- Therapeutic use
description The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was found
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
peer-reviewed
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/26257
url http://hdl.handle.net/10256/26257
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jinorgbio.2021.111403
info:eu-repo/semantics/altIdentifier/issn/0162-0134
info:eu-repo/semantics/altIdentifier/eissn/1873-3344
dc.rights.none.fl_str_mv Reconeixement-NoComercial-SenseObraDerivada 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Reconeixement-NoComercial-SenseObraDerivada 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv © Journal of Inorganic Biochemistry, 2021, vol. 218, art.núm.111403
Articles publicats (D-B)
Leal, Jorge Santos, Lúcia H.M.L.M. Fernández-Aroca, Diego M. Cuevas-Vicario, José Vicente Martínez, Ma Ángeles Massaguer i Vall-llovera, Anna Jalón, Félix A. Ruiz-Hidalgo, María José Sánchez-Prieto, Ricardo Rodríguez, Ana maría Blanco Castañeda Peñalvo, Gregorio Dura, Gema Carriõn, María Carmen Barrabés Vera, Sílvia Manzano, Blanca R. 2021 Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential. Journal of Inorganic Biochemistry 218 art.núm.111403
reponame:Recercat. Dipósit de la Recerca de Catalunya
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instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
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