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

Espadinha, Margarida; Barcherini, Valentina; Gonçalves, Lídia; Molins, Elies; Antunes, Alexandra M. M.; Santos, Maria M. M.

http://hdl.handle.net/10451/59304

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Autores

Espadinha, Margarida

Barcherini, Valentina

Gonçalves, Lídia

Molins, Elies

Antunes, Alexandra M. M.

Santos, Maria M. M.

Resumo(s)

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.

Descrição

© 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/).

Palavras-chave

anticancer agents cytotoxicity enantioselective synthesis gastric adenocarcinoma tryptophanol

URI

http://hdl.handle.net/10451/59304

Citação

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

Editora

MDPI

DOI

10.3390/ph14030208

Coleções

FF - CiênciaVitae - Faculdade de Farmácia

Licença CC

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