Toxicity and structure-activity relationship (SAR) of alpha,beta-dehydroamino acids against human cancer cell lines

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Videira, RA (Autor) Outra; Paula B Andrade (Autor) FFUP; Monteiro, LS (Autor) Outra; Patricia Valentao (Autor) FFUP; Ferreira, PMT (Autor) Outra; David M Pereira (Autor) FFUP

Revista

Título: Toxicology in Vitro

Vol. 47

Páginas: 26-37

ISSN: 0887-2333

Editora: Elsevier

Indexação

ISI Web of Knowledge - 3 Citações

Scopus - 6 Citações

Outras Informações

ID Authenticus: P-00N-6MG

DOI: 10.1016/j.tiv.2017.10.027

Abstract (EN): A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells. Four alpha,beta-dehydroalanine derivatives, with IC50 < 62.5 mu M, were selected to investigate the pathways by which these compounds promote cell death. All compounds, at their IC50 concentrations, were able to induce apoptosis in both AGS and SH-SY5Y cell lines. In both cell lines, loss of mitochondria] membrane potential (Delta psi m) was found and caspase activity was increased, namely endoplasmic reticulum-resident caspase-4 in AGS cells and caspase-3/7 in SH-SY5Y cells. When evaluated in a non-cancer cell line, the molecules displayed no to low toxicity, thus suggesting some degree of selectivity for cancer cells. The results indicate that a,p-dehydroalanine derivatives can be considered a future resource of compounds able to work as anticancer drugs.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12