Toward the selective delivery of chemotherapeutics into tumor cells by targeting peptide transporters: Tailored gold-based anticancer peptidomimetics

Morelle Negom Kouodom, Luca Ronconi, Marta Celegato, Chiara Nardon, Luciano Marchiò, Q. Ping Dou, Donatella Aldinucci, Fernando Formaggio, Dolores Fregona

Research output: Contribution to journalArticle

Abstract

Complexes [Au IIIX 2(dtc-Sar-AA-O(t-Bu))] (AA = Gly, X = Br (1)/Cl (2); AA = Aib, X = Br (3)/Cl (4); AA = l-Phe, X = Br (5)/Cl (6)) were designed on purpose in order to obtain gold(III)-based anticancer peptidomimetics that might specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy, and the crystal structure of [Au IIIBr 2(dtc-Sar-Aib-O(t- Bu))] (3) was solved and refined. According to in vitro cytotoxicity studies, the Aib-containing complexes 3 and 4 turned out to be the most effective toward all the human tumor cell lines evaluated (PC3, DU145, 2008, C13, and L540), reporting IC 50 values much lower than that of cisplatin. Remarkably, they showed no cross-resistance with cisplatin itself and were proved to inhibit tumor cell proliferation by inducing either apoptosis or late apoptosis/necrosis depending on the cell lines. Biological results are here reported and discussed in terms of the structure-activity relationship.

Original languageEnglish
Pages (from-to)2212-2226
Number of pages15
JournalJournal of Medicinal Chemistry
Volume55
Issue number5
DOIs
Publication statusPublished - Mar 8 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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