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https://hdl.handle.net/1822/48095
Título: | Toxicity and structure-activity relationship (SAR) of α, β-dehydroamino acids against human cancer cell lines |
Autor(es): | Pereira, David M. Videira, Romeu A. Andrade, Paula B. Monteiro, Luís S. Valentão, Patrícia Ferreira, Paula M. T. |
Palavras-chave: | Dehydroamino acids Toxicological profile Apoptosis Caspases Therapeutic agents Structure-activity relationship (SAR) |
Data: | 2018 |
Editora: | Elsevier |
Revista: | Toxicology in Vitro |
Citação: | Romeu A. Videira, Paula B. Andrade, Luís S. Monteiro, Patrícia Valentão, Paula M.T. Ferreira, David M. Pereira, Toxicology in Vitro 47 (2018) 26–37 |
Resumo(s): | 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 α,β- dehydroalanine derivatives, with IC50 < 62.5 μM, 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 mitochondrial membrane potential (ΔΨm) 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 α,β-dehydroalanine derivatives can be considered a future resource of compounds able to work as anticancer drugs. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/48095 |
DOI: | 10.1016/j.tiv.2017.10.027 |
ISSN: | 0887-2333 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CDQuim - Artigos (Papers) |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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2018-Toxicology in vitro.pdf | 206,87 kB | Adobe PDF | Ver/Abrir |