Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer

A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID sc...

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Autores: Ramos Inza, Sandra, Encío Martínez, Ignacio, Raza, Asif, Sharma, Arun K., Sanmartín, Carmen, Plano, Daniel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/45036
Acceso en línea:https://hdl.handle.net/2454/45036
Access Level:acceso abierto
Palabra clave:Apoptosis
Cytotoxicity
NSAID
Selenium
Selenoester
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spelling Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancerRamos Inza, SandraEncío Martínez, IgnacioRaza, AsifSharma, Arun K.Sanmartín, CarmenPlano, DanielApoptosisCytotoxicityNSAIDSeleniumSelenoesterA total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI's panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer.This work was financially supported by the Plan de Investigación de la Universidad de Navarra, PIUNA (2018-19), and the Department of Pharmacology and Penn State Cancer Institute of the Penn State College of Medicine. Sandra Ramos-Inza also acknowledges the FPU program from the Spanish Ministry of Universities for a Ph.D. fellowship (FPU18/04679) and a mobility grant (EST19/00898).ElsevierCiencias de la SaludOsasun ZientziakInstitute for Multidisciplinary Research in Applied Biology - IMAB2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/mswordhttps://hdl.handle.net/2454/45036reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad Pública de NavarraInglésinfo:eu-repo/grantAgreement///FPU18%2F04679© 2022 The Authors. This is an open access article under the CC BY-NC-ND license.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/450362026-06-17T12:41:47Z
dc.title.none.fl_str_mv Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
title Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
spellingShingle Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
Ramos Inza, Sandra
Apoptosis
Cytotoxicity
NSAID
Selenium
Selenoester
title_short Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
title_full Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
title_fullStr Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
title_full_unstemmed Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
title_sort Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
dc.creator.none.fl_str_mv Ramos Inza, Sandra
Encío Martínez, Ignacio
Raza, Asif
Sharma, Arun K.
Sanmartín, Carmen
Plano, Daniel
author Ramos Inza, Sandra
author_facet Ramos Inza, Sandra
Encío Martínez, Ignacio
Raza, Asif
Sharma, Arun K.
Sanmartín, Carmen
Plano, Daniel
author_role author
author2 Encío Martínez, Ignacio
Raza, Asif
Sharma, Arun K.
Sanmartín, Carmen
Plano, Daniel
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
Institute for Multidisciplinary Research in Applied Biology - IMAB
dc.subject.none.fl_str_mv Apoptosis
Cytotoxicity
NSAID
Selenium
Selenoester
topic Apoptosis
Cytotoxicity
NSAID
Selenium
Selenoester
description A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI's panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer.
publishDate 2022
dc.date.none.fl_str_mv 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/2454/45036
url https://hdl.handle.net/2454/45036
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement///FPU18%2F04679
dc.rights.none.fl_str_mv © 2022 The Authors. This is an open access article under the CC BY-NC-ND license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2022 The Authors. This is an open access article under the CC BY-NC-ND license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/msword
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad Pública de Navarra
instname_str Universidad Pública de Navarra
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
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