Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity

Novel derivatives of carnosic acid 1 with ester or carbamate groups at C-20 and derivatives with these functional groups combined with benzylic modifications (C-7) were synthesized and evaluated in a colorectal cancer cell line (HCT116). Compound 8, which featured a butyl ester at C-20 and a carbony...

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Authors: S. P. Moura, Sara P., Cascante i Serratosa, Marta, Rufino, Ismael, Guedes, Rita C., Marín Martínez, Silvia, Salvador, Jorge A. R.
Format: article
Status:Published version
Publication Date:2025
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:2445/227824
Online Access:https://hdl.handle.net/2445/227824
Access Level:Open access
Keyword:Cicle cel·lular
Cèl·lules canceroses
Cell cycle
Cancer cells
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spelling Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activityS. P. Moura, Sara P.Cascante i Serratosa, MartaRufino, IsmaelGuedes, Rita C.Marín Martínez, SilviaSalvador, Jorge A. R.Cicle cel·lularCèl·lules cancerosesCell cycleCancer cellsNovel derivatives of carnosic acid 1 with ester or carbamate groups at C-20 and derivatives with these functional groups combined with benzylic modifications (C-7) were synthesized and evaluated in a colorectal cancer cell line (HCT116). Compound 8, which featured a butyl ester at C-20 and a carbonyl group at C-7, and compound 17, which featured a 2-methylpropyl carbamate at C-20, achieved the best results in HCT116 cells. Compounds 8 and 17 also demonstrated better ability to inhibit the growth of other cancer cell lines than CA 1. In general, the best results were achieved with compound 17, which exhibited higher potency against SW480 cells (IC<sub>50</sub> = 6.3 μM). This compound also showed selectivity for cancer cells compared to normal cells. Compound 17 was subjected to additional studies to elucidate the mechanism responsible for its antiproliferative activity in SW480 cells. At 24 h, compound 17 arrested the cell cycle at the G0/G1 phase by decreasing the CDK4/CDK6 levels. It also reduced ROS levels by increasing the expression of SOD2/MnSOD. However, at 48 h, compound 17 induced cell cycle arrest in the S phase and increased ROS levels. At 72 h, compound 17 elevated the ROS levels without inducing cell cycle arrest. Additionally, molecular docking studies showed that compound 17 establishes several interactions with the amino acids of the CDK6 active site. In conclusion, compound 17 is a promising candidate for the development of novel anticancer drugs.Royal Society of Chemistry2026202620252026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/227824Articles 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/10.1039/d5ra02441bRSC Advances, 2025, vol. 15, num.44, p. 36861-36878https://doi.org/10.1039/d5ra02441bcc-by (c) Moura, S.P.S.P. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2278242026-05-29T05:05:01Z
dc.title.none.fl_str_mv Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
title Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
spellingShingle Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
S. P. Moura, Sara P.
Cicle cel·lular
Cèl·lules canceroses
Cell cycle
Cancer cells
title_short Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
title_full Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
title_fullStr Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
title_full_unstemmed Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
title_sort Synthesis and biological evaluation of novel carnosic acid derivatives with anticancer activity
dc.creator.none.fl_str_mv S. P. Moura, Sara P.
Cascante i Serratosa, Marta
Rufino, Ismael
Guedes, Rita C.
Marín Martínez, Silvia
Salvador, Jorge A. R.
author S. P. Moura, Sara P.
author_facet S. P. Moura, Sara P.
Cascante i Serratosa, Marta
Rufino, Ismael
Guedes, Rita C.
Marín Martínez, Silvia
Salvador, Jorge A. R.
author_role author
author2 Cascante i Serratosa, Marta
Rufino, Ismael
Guedes, Rita C.
Marín Martínez, Silvia
Salvador, Jorge A. R.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Cicle cel·lular
Cèl·lules canceroses
Cell cycle
Cancer cells
topic Cicle cel·lular
Cèl·lules canceroses
Cell cycle
Cancer cells
description Novel derivatives of carnosic acid 1 with ester or carbamate groups at C-20 and derivatives with these functional groups combined with benzylic modifications (C-7) were synthesized and evaluated in a colorectal cancer cell line (HCT116). Compound 8, which featured a butyl ester at C-20 and a carbonyl group at C-7, and compound 17, which featured a 2-methylpropyl carbamate at C-20, achieved the best results in HCT116 cells. Compounds 8 and 17 also demonstrated better ability to inhibit the growth of other cancer cell lines than CA 1. In general, the best results were achieved with compound 17, which exhibited higher potency against SW480 cells (IC<sub>50</sub> = 6.3 μM). This compound also showed selectivity for cancer cells compared to normal cells. Compound 17 was subjected to additional studies to elucidate the mechanism responsible for its antiproliferative activity in SW480 cells. At 24 h, compound 17 arrested the cell cycle at the G0/G1 phase by decreasing the CDK4/CDK6 levels. It also reduced ROS levels by increasing the expression of SOD2/MnSOD. However, at 48 h, compound 17 induced cell cycle arrest in the S phase and increased ROS levels. At 72 h, compound 17 elevated the ROS levels without inducing cell cycle arrest. Additionally, molecular docking studies showed that compound 17 establishes several interactions with the amino acids of the CDK6 active site. In conclusion, compound 17 is a promising candidate for the development of novel anticancer drugs.
publishDate 2025
dc.date.none.fl_str_mv 2025
2026
2026
2026
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/2445/227824
url https://hdl.handle.net/2445/227824
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/10.1039/d5ra02441b
RSC Advances, 2025, vol. 15, num.44, p. 36861-36878
https://doi.org/10.1039/d5ra02441b
dc.rights.none.fl_str_mv cc-by (c) Moura, S.P.S.P. et al., 2025
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., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 18 p.
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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
_version_ 1869406363705147392
score 15.223283

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