Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity

A series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carn...

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Detalles Bibliográficos
Autores: S. P. Moura, Sara P., Marín Martínez, Silvia, Rufino, Ismael, Guedes, Rita C., Cascante i Serratosa, Marta, Salvador, Jorge A. R.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
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:2445/218057
Acceso en línea:https://hdl.handle.net/2445/218057
Access Level:acceso abierto
Palabra clave:Cicle cel·lular
Urea
Cèl·lules canceroses
Cell cycle
Cancer cells
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spelling Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer ActivityS. P. Moura, Sara P.Marín Martínez, SilviaRufino, IsmaelGuedes, Rita C.Cascante i Serratosa, MartaSalvador, Jorge A. R.Cicle cel·lularUreaCèl·lules cancerosesCell cycleUreaCancer cellsA series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid 1. The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2). Derivative 14 consistently demonstrated the highest activity across all tested cancer cell lines, showing selectivity for cancer cells over normal cells. Further investigation of the mechanism of action in SW480 cells revealed that compound 14 induced cell cycle arrest at the G0/G1 phase by downregulating CDK4 and CDK6. Molecular docking studies revealed that compound 14 established several interactions with key residues in the active site of CDK6. Additionally, compound 14 also reduced ROS production. In summary, our results strongly indicate that compound 14 has potential as a lead compound in the development of innovative anticancer drugs.MDPI2025202520242025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion29 p.application/pdfhttps://hdl.handle.net/2445/218057Articles publicats en revistes (Bioquímica i Biomedicina Molecular)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/10.3390/ijms252413332International Journal of Molecular Sciences, 2024, vol. 25, num.24, p. 1-29https://doi.org/10.3390/ijms252413332cc-by (c) Moura, S.P.S.P. et al., 2024http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2180572026-05-29T05:05:01Z
dc.title.none.fl_str_mv Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
title Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
spellingShingle Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
S. P. Moura, Sara P.
Cicle cel·lular
Urea
Cèl·lules canceroses
Cell cycle
Urea
Cancer cells
title_short Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
title_full Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
title_fullStr Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
title_full_unstemmed Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
title_sort Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
dc.creator.none.fl_str_mv S. P. Moura, Sara P.
Marín Martínez, Silvia
Rufino, Ismael
Guedes, Rita C.
Cascante i Serratosa, Marta
Salvador, Jorge A. R.
author S. P. Moura, Sara P.
author_facet S. P. Moura, Sara P.
Marín Martínez, Silvia
Rufino, Ismael
Guedes, Rita C.
Cascante i Serratosa, Marta
Salvador, Jorge A. R.
author_role author
author2 Marín Martínez, Silvia
Rufino, Ismael
Guedes, Rita C.
Cascante i Serratosa, Marta
Salvador, Jorge A. R.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cicle cel·lular
Urea
Cèl·lules canceroses
Cell cycle
Urea
Cancer cells
topic Cicle cel·lular
Urea
Cèl·lules canceroses
Cell cycle
Urea
Cancer cells
description A series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid 1. The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2). Derivative 14 consistently demonstrated the highest activity across all tested cancer cell lines, showing selectivity for cancer cells over normal cells. Further investigation of the mechanism of action in SW480 cells revealed that compound 14 induced cell cycle arrest at the G0/G1 phase by downregulating CDK4 and CDK6. Molecular docking studies revealed that compound 14 established several interactions with key residues in the active site of CDK6. Additionally, compound 14 also reduced ROS production. In summary, our results strongly indicate that compound 14 has potential as a lead compound in the development of innovative anticancer drugs.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
2025
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/2445/218057
url https://hdl.handle.net/2445/218057
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/10.3390/ijms252413332
International Journal of Molecular Sciences, 2024, vol. 25, num.24, p. 1-29
https://doi.org/10.3390/ijms252413332
dc.rights.none.fl_str_mv cc-by (c) Moura, S.P.S.P. et al., 2024
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Moura, S.P.S.P. et al., 2024
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 29 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
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 15.811543

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