Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma

Detalhes bibliográficos
Autor(a) principal: Espadinha, Margarida
Data de Publicação: 2021
Outros Autores: Barcherini, Valentina, Gonçalves, Lídia, Molins, Elies, Antunes, Alexandra M. M., Santos, Maria M. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/59304
Resumo: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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spelling Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinomaanticancer agentscytotoxicityenantioselective synthesisgastric adenocarcinomatryptophanol© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Gastric cancer is one of the deadliest cancers in modern societies, so there is a high level of interest in discovering new drugs for this malignancy. Previously, we demonstrated the ability of tryptophanol-derived polycyclic compounds to activate the tumor suppressor protein p53, a relevant therapeutic target in cancer. In this work, we developed a novel series of enantiomerically pure tryptophanol-derived small molecules to target human gastric adenocarcinoma (AGS) cells. From an initial screening of fourteen compounds in AGS cell line, a hit compound was selected for optimization, leading to two derivatives selective for AGS gastric cells over other types of cancer cells (MDA-MB-231, A-549, DU-145, and MG-63). More importantly, the compounds were non-toxic in normal cells (HEK 293T). Additionally, we show that the growth inhibition of AGS cells induced by these compounds is mediated by apoptosis. Stability studies in human plasma and human liver microsomes indicate that the compounds are stable, and that the major metabolic transformations of these molecules are mono- and di-hydroxylation of the indole ring.This research was funded by FCT (Fundação para a Ciência e a Tecnologia) through iMed.ULisboa (UIDB/04138/2020), CQE (UID/QUI/00100/2020), project PTDC/QUI-QOR/29664/2017, principal investigator grants CEECIND/02001/2017 (A. M. M. Antunes), and CEECIND/03143/2017 (L. M. Gonçalves), and PhD fellowships SFRH/BD/117931/2016 (M. Espadinha) and PD/BD/143126/2019 (V. Barcherini), and funded by Severo Ochoa FunFuture CEX2019-917-S.MDPIRepositório da Universidade de LisboaEspadinha, MargaridaBarcherini, ValentinaGonçalves, LídiaMolins, EliesAntunes, Alexandra M. M.Santos, Maria M. M.2023-09-14T15:52:18Z2021-03-022023-02-27T15:53:52Z2021-03-02T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/59304engEspadinha M, Barcherini V, Gonçalves LM, Molins E, Antunes AMM, Santos MMM. Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma. Pharmaceuticals. 2021 Mar 2;14(3):208. Available from: http://dx.doi.org/10.3390/ph14030208cv-prod-242094010.3390/ph14030208info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-12-04T01:18:19Zoai:repositorio.ul.pt:10451/59304Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:07:00.190437Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
title Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
spellingShingle Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
Espadinha, Margarida
anticancer agents
cytotoxicity
enantioselective synthesis
gastric adenocarcinoma
tryptophanol
title_short Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
title_full Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
title_fullStr Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
title_full_unstemmed Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
title_sort Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
author Espadinha, Margarida
author_facet Espadinha, Margarida
Barcherini, Valentina
Gonçalves, Lídia
Molins, Elies
Antunes, Alexandra M. M.
Santos, Maria M. M.
author_role author
author2 Barcherini, Valentina
Gonçalves, Lídia
Molins, Elies
Antunes, Alexandra M. M.
Santos, Maria M. M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Espadinha, Margarida
Barcherini, Valentina
Gonçalves, Lídia
Molins, Elies
Antunes, Alexandra M. M.
Santos, Maria M. M.
dc.subject.por.fl_str_mv anticancer agents
cytotoxicity
enantioselective synthesis
gastric adenocarcinoma
tryptophanol
topic anticancer agents
cytotoxicity
enantioselective synthesis
gastric adenocarcinoma
tryptophanol
description © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
publishDate 2021
dc.date.none.fl_str_mv 2021-03-02
2021-03-02T00:00:00Z
2023-09-14T15:52:18Z
2023-02-27T15:53:52Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/59304
url http://hdl.handle.net/10451/59304
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Espadinha M, Barcherini V, Gonçalves LM, Molins E, Antunes AMM, Santos MMM. Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma. Pharmaceuticals. 2021 Mar 2;14(3):208. Available from: http://dx.doi.org/10.3390/ph14030208
cv-prod-2420940
10.3390/ph14030208
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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