COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents

Photodynamic therapy (PDT) for cancer treatment has drawn increased attention over the last decades. Herein, we introduce a novel family of low-molecular-weight coumarins as potential PDT anticancer tools. Through a systematic study with a library of 15 compounds, we have established a detailed stru...

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Authors: Ortega Forte, Enrique, Rovira, Anna, Gandioso, Albert, Bonelli Blasco, Joaquin Daniel, Bosch Marimon, Manel, Ruiz, José, Marchán Sancho, Vicente
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/183273
Online Access:https://hdl.handle.net/2445/183273
Access Level:Open access
Keyword:Cumarines
Medicaments antineoplàstics
Autofàgia
Coumarins
Antineoplastic agents
Autophagy
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spelling COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer AgentsOrtega Forte, EnriqueRovira, AnnaGandioso, AlbertBonelli Blasco, Joaquin DanielBosch Marimon, ManelRuiz, JoséMarchán Sancho, VicenteCumarinesMedicaments antineoplàsticsAutofàgiaCoumarinsAntineoplastic agentsAutophagyPhotodynamic therapy (PDT) for cancer treatment has drawn increased attention over the last decades. Herein, we introduce a novel family of low-molecular-weight coumarins as potential PDT anticancer tools. Through a systematic study with a library of 15 compounds, we have established a detailed structure−activity relationship rationale, which allowed the selection of three lead compounds exhibiting effective in vitro anticancer activities upon visible-light irradiation in both normoxia and hipoxia (phototherapeutic indexes up to 71) and minimal toxicity toward normal cells. Acting as excellent theranostic agents targeting mitochondria, the mechanism of action of the photosensitizers has been investigated in detail in HeLa cells. The generation of cytotoxic reactive oxygen species, which has been found to be a major contributor of the coumarins' phototoxicity, and the induction of apoptosis and/or autophagy have been identified as the cell death modes triggered after irradiation with low doses of visible light.American Chemical Society2022202220212022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion12 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/183273Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1021/acs.jmedchem.1c01254Journal of Medicinal Chemistry, 2021, vol. 64, num. 23, p. 17209-17220https://doi.org/10.1021/acs.jmedchem.1c01254cc-by (c) Ortega-Forte, Enrique, et al., 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1832732026-05-29T05:05:01Z
dc.title.none.fl_str_mv COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
title COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
spellingShingle COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
Ortega Forte, Enrique
Cumarines
Medicaments antineoplàstics
Autofàgia
Coumarins
Antineoplastic agents
Autophagy
title_short COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
title_full COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
title_fullStr COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
title_full_unstemmed COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
title_sort COUPY Coumarins as Novel Mitochondria-Targeted Photodynamic Therapy Anticancer Agents
dc.creator.none.fl_str_mv Ortega Forte, Enrique
Rovira, Anna
Gandioso, Albert
Bonelli Blasco, Joaquin Daniel
Bosch Marimon, Manel
Ruiz, José
Marchán Sancho, Vicente
author Ortega Forte, Enrique
author_facet Ortega Forte, Enrique
Rovira, Anna
Gandioso, Albert
Bonelli Blasco, Joaquin Daniel
Bosch Marimon, Manel
Ruiz, José
Marchán Sancho, Vicente
author_role author
author2 Rovira, Anna
Gandioso, Albert
Bonelli Blasco, Joaquin Daniel
Bosch Marimon, Manel
Ruiz, José
Marchán Sancho, Vicente
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cumarines
Medicaments antineoplàstics
Autofàgia
Coumarins
Antineoplastic agents
Autophagy
topic Cumarines
Medicaments antineoplàstics
Autofàgia
Coumarins
Antineoplastic agents
Autophagy
description Photodynamic therapy (PDT) for cancer treatment has drawn increased attention over the last decades. Herein, we introduce a novel family of low-molecular-weight coumarins as potential PDT anticancer tools. Through a systematic study with a library of 15 compounds, we have established a detailed structure−activity relationship rationale, which allowed the selection of three lead compounds exhibiting effective in vitro anticancer activities upon visible-light irradiation in both normoxia and hipoxia (phototherapeutic indexes up to 71) and minimal toxicity toward normal cells. Acting as excellent theranostic agents targeting mitochondria, the mechanism of action of the photosensitizers has been investigated in detail in HeLa cells. The generation of cytotoxic reactive oxygen species, which has been found to be a major contributor of the coumarins' phototoxicity, and the induction of apoptosis and/or autophagy have been identified as the cell death modes triggered after irradiation with low doses of visible light.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/183273
url https://hdl.handle.net/2445/183273
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1021/acs.jmedchem.1c01254
Journal of Medicinal Chemistry, 2021, vol. 64, num. 23, p. 17209-17220
https://doi.org/10.1021/acs.jmedchem.1c01254
dc.rights.none.fl_str_mv cc-by (c) Ortega-Forte, Enrique, et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ortega-Forte, Enrique, et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
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 Articles publicats en revistes (Química Inorgànica i Orgànica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
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
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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