Abstract
A small and focused library of 22 dipeptides derived from N,N-dibenzylglutamic acid α- and γ-benzyl esters was prepared in a straightforward manner. The evaluation of the antiproliferative activity in the human solid tumor cell lines HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast), and WiDr (colon) provided γ-glutamyl methionine (GI50 = 6.0–41 μM) and α-glutamyl proline (GI50 = 7.5–18 μM) as lead compounds. In particular, glutamyl serine and glutamyl proline dipeptides were more active in the resistant cancer cell line WiDr than the conventional anticancer drugs cisplatin and etoposide. Glutamyl tryptophan dipeptides did not affect cell growth of HBL-100, while in T-47D cells, proliferation was inhibited. This result might be attributed to the inhibition of the ATB0,+ transporter.
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Acknowledgments
Co-financed by the EU Research Potential (FP7-REGPOT-2012-CT2012-31637-IMBRAIN), the European Regional Development Fund (FEDER), the Spanish MINECO (CTQ2011-28417-C02-01 and Instituto de Salud Carlos III PI11/00840). G.S.-D. thanks the EU Social Fund (FSE) and the Canary Islands ACIISI for a predoctoral grant.
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Silveira-Dorta, G., Martín, V.S. & Padrón, J.M. Synthesis and antiproliferative activity of glutamic acid-based dipeptides. Amino Acids 47, 1527–1532 (2015). https://doi.org/10.1007/s00726-015-1987-0
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DOI: https://doi.org/10.1007/s00726-015-1987-0