Publication Type Journal Article
Title Tryptophanol-Derived Oxazolopyrrolidone Lactams as Potential Anticancer Agents against Gastric Adenocarcinoma
Authors Margarida Espadinha Valentina Barcherini Lidia Goncalves Elies Molins Alexandra Maria Moita Antunes Maria M. M. Santos
Groups BIOMOL
Journal PHARMACEUTICALS
Year 2021
Month March
Volume 14
Number 3
Pages
Abstract 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.
DOI http://dx.doi.org/10.3390/ph14030208
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Publisher
Book Title
ISSN
EISSN 1424-8247
Conference Name
Bibtex ID ISI:000634076500001
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