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; Encío Martínez, Ignacio; Raza, Asif; Sharma, Arun K.; Sanmartín, Carmen; Plano, Daniel

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.contributor.author	Ramos Inza, Sandra
dc.contributor.author	Encío Martínez, Ignacio
dc.contributor.author	Raza, Asif
dc.contributor.author	Sharma, Arun K.
dc.contributor.author	Sanmartín, Carmen
dc.contributor.author	Plano, Daniel
dc.contributor.department	Ciencias de la Salud	es_ES
dc.contributor.department	Osasun Zientziak	eu
dc.contributor.department	Institute for Multidisciplinary Research in Applied Biology - IMAB	en
dc.date.accessioned	2023-04-04T18:01:34Z
dc.date.available	2023-04-04T18:01:34Z
dc.date.issued	2022
dc.date.updated	2023-04-04T17:55:50Z
dc.description.abstract	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.	en
dc.description.sponsorship	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).	en
dc.format.mimetype	application/pdf	en
dc.format.mimetype	application/msword	en
dc.identifier.citation	Ramos-Inza, S., Encío, I., Raza, A., Sharma, A. K., Sanmartín, C., & Plano, D. (2022). Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer. European Journal of Medicinal Chemistry, 244, 114839. https://doi.org/10.1016/j.ejmech.2022.114839	en
dc.identifier.doi	10.1016/j.ejmech.2022.114839
dc.identifier.issn	0223-5234
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/45036
dc.language.iso	eng	en
dc.publisher	Elsevier	es_ES
dc.relation.ispartof	European Journal of Medicinal Chemistry, 244 (2022), 114839	en
dc.relation.projectID	info:eu-repo/grantAgreement///FPU18%2F04679/
dc.relation.publisherversion	https://doi.org/10.1016/j.ejmech.2022.114839
dc.rights	© 2022 The Authors. This is an open access article under the CC BY-NC-ND license.	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject	Apoptosis	en
dc.subject	Cytotoxicity	en
dc.subject	NSAID	en
dc.subject	Selenium	en
dc.subject	Selenoester	en
dc.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	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion
dspace.entity.type	Publication
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