On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions

A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human...

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Autores: Escolà Jané, Anna, Crespo Vicente, Margarita Ma., López Martínez, Ma. Concepción, Quirante Serrano, Josefina, Jayaraman, Anusha, Halil Polat, Ibrahim, Badía Palacín, Josefa, Baldomà Llavinés, Laura, Cascante i Serratosa, Marta
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/165158
Acceso en línea:https://hdl.handle.net/2445/165158
Access Level:acceso abierto
Palabra clave:Platí
Medicaments antineoplàstics
Platinum
Antineoplastic agents
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spelling On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positionsEscolà Jané, AnnaCrespo Vicente, Margarita Ma.López Martínez, Ma. ConcepciónQuirante Serrano, JosefinaJayaraman, AnushaHalil Polat, IbrahimBadía Palacín, JosefaBaldomà Llavinés, LauraCascante i Serratosa, MartaPlatíMedicaments antineoplàsticsPlatinumAntineoplastic agentsA series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to -1.570 V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment. Actually ascorbic acid was not able to reduce complex 3a', the most prone to be reduced according its reduction potential, over a period of one week. These results suggest an intrinsic activity for the investigated platinum(IV) complexes (3a, 3a' and 3b'), which exhibit a remarkable cytotoxicity effectiveness (with IC50 values in the low micromolar range), even greater than that of cisplatin. The IC50 for A-549 lung cells and clog P values were found to follow the same trend: 3b' > 3a' > 3a. However, no correlation was observed between reduction potential and in vitro activity. As a representative example, cyclometallated platinum(IV) compound 3a', exercise its antiproliferative activity directly over non-microcytic A-549 lung cancer cells through a mixture of cell cycle arrest (13% arrest at G1 phase and 46% arrest at G2 phase) and apoptosis induction (increase of early apoptosis by 30 times with regard to control). To gain further insights into the mode of action of the investigated platinum(IV) complexes, drug uptake, cathepsin B inhibition and ROS generation were also evaluated. Interestingly an increased ROS generation could be related with the antiproliferative activity of the cyclometallated platinum(IV) series under study in the cisplatin-resistant A-549 lung and HCT-116 cancer cell lines.Elsevier Ltd2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/165158Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.bmc.2016.09.037Bioorganic & Medicinal Chemistry, 2016, vol. 24, num. 22, p. 5804-5815https://doi.org/10.1016/j.bmc.2016.09.037cc-by-nc-nd (c) Elsevier Ltd, 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1651582026-05-27T06:46:51Z
dc.title.none.fl_str_mv On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
title On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
spellingShingle On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
Escolà Jané, Anna
Platí
Medicaments antineoplàstics
Platinum
Antineoplastic agents
title_short On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
title_full On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
title_fullStr On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
title_full_unstemmed On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
title_sort On the stability and biological behavior of cyclometallated Pt(IV) complexes with halido and aryl ligands in the axial positions
dc.creator.none.fl_str_mv Escolà Jané, Anna
Crespo Vicente, Margarita Ma.
López Martínez, Ma. Concepción
Quirante Serrano, Josefina
Jayaraman, Anusha
Halil Polat, Ibrahim
Badía Palacín, Josefa
Baldomà Llavinés, Laura
Cascante i Serratosa, Marta
author Escolà Jané, Anna
author_facet Escolà Jané, Anna
Crespo Vicente, Margarita Ma.
López Martínez, Ma. Concepción
Quirante Serrano, Josefina
Jayaraman, Anusha
Halil Polat, Ibrahim
Badía Palacín, Josefa
Baldomà Llavinés, Laura
Cascante i Serratosa, Marta
author_role author
author2 Crespo Vicente, Margarita Ma.
López Martínez, Ma. Concepción
Quirante Serrano, Josefina
Jayaraman, Anusha
Halil Polat, Ibrahim
Badía Palacín, Josefa
Baldomà Llavinés, Laura
Cascante i Serratosa, Marta
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Platí
Medicaments antineoplàstics
Platinum
Antineoplastic agents
topic Platí
Medicaments antineoplàstics
Platinum
Antineoplastic agents
description A series of cyclometallated platinum(IV) compounds (3a, 3a' and 3b') with a meridional [C,N,N'] terdentate ligand, featuring an halido and an aryl group in the axial positions has been evaluated for electrochemical reduction and preliminary biological behavior against a panel of human adenocarcinoma (A-549 lung, HCT-116 colon, and MCF-7 breast) cell lines and the normal bronquial epithelial BEAS-2B cells. Cathodic reduction potentials (shifting from -1.463 to -1.570 V) reveal that the platinum(IV) compounds under study would be highly reluctant to be reduced in a biological environment. Actually ascorbic acid was not able to reduce complex 3a', the most prone to be reduced according its reduction potential, over a period of one week. These results suggest an intrinsic activity for the investigated platinum(IV) complexes (3a, 3a' and 3b'), which exhibit a remarkable cytotoxicity effectiveness (with IC50 values in the low micromolar range), even greater than that of cisplatin. The IC50 for A-549 lung cells and clog P values were found to follow the same trend: 3b' > 3a' > 3a. However, no correlation was observed between reduction potential and in vitro activity. As a representative example, cyclometallated platinum(IV) compound 3a', exercise its antiproliferative activity directly over non-microcytic A-549 lung cancer cells through a mixture of cell cycle arrest (13% arrest at G1 phase and 46% arrest at G2 phase) and apoptosis induction (increase of early apoptosis by 30 times with regard to control). To gain further insights into the mode of action of the investigated platinum(IV) complexes, drug uptake, cathepsin B inhibition and ROS generation were also evaluated. Interestingly an increased ROS generation could be related with the antiproliferative activity of the cyclometallated platinum(IV) series under study in the cisplatin-resistant A-549 lung and HCT-116 cancer cell lines.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/165158
url https://hdl.handle.net/2445/165158
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.bmc.2016.09.037
Bioorganic & Medicinal Chemistry, 2016, vol. 24, num. 22, p. 5804-5815
https://doi.org/10.1016/j.bmc.2016.09.037
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier Ltd, 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier Ltd, 2016
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
dc.source.none.fl_str_mv Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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