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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

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

Journal

Title: Toxicology in Vitro

Vol. 47

Pages: 26-37

ISSN: 0887-2333

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 6 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12