title: Synthesis and antiproliferative activity of glutamic acid-based dipeptides.
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 ATB(0,+) transporter.
authors.affiliation: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206, La Laguna, Spain.
authors.forename: Gastón
authors.initials: G
authors.lastname: Silveira-Dorta
authors.forename: Víctor S
authors.initials: VS
authors.lastname: Martín
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; D018698:Glutamic Acid