Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy

Morelle Negom Kouodom, Giulia Boscutti, Marta Celegato, Marco Crisma, Sergio Sitran, Donatella Aldinucci, Fernando Formaggio, Luca Ronconi, Dolores Fregona

Research output: Contribution to journalArticlepeer-review


As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [AuIIIX2(dtc-Sar-l-Ser(t-Bu)- O(t-Bu))] (X = Br (1a)/Cl (1b)), [AuIIIX2(dtc-AA-Aib 2-O(t-Bu))] (AA = Sar (sarcosine, N-methylglycine), X = Br (2a)/Cl (2b); AA = d,l-Pro, X = Br (3a)/Cl (3b)), [AuIIIX2(dtc- Sar-Aib3-O(t-Bu))] (X = Br (4a)/Cl (4b)), and [AuIIIX 2(dtc-Sar-Aib3-Gly-OEt)] (X = Br (5a)/Cl (5b)) (Aib = alpha-aminoisobutyric acid, 2-methylalanine) were designed to obtain metal-based peptidomimetics that may specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several human tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in vitro cytotoxicity studies, complex [Au IIICl2(dtc-d,l-Pro-Aib2-O(t-Bu))] (3b) turned out to be the most effective toward the four human tumor cell lines evaluated (PC3, 2008, C13, and L540), for which the IC50 values were lower than cisplatin. Remarkably, it showed no cross-resistance with cisplatin itself and was proved to inhibit tumor cell proliferation by inducing almost exclusively late apoptosis/necrosis. Biological results are here reported and discussed in terms of the structure-activity relationship.

Original languageEnglish
Pages (from-to)248-260
Number of pages13
JournalJournal of Inorganic Biochemistry
Publication statusPublished - Dec 2012


  • Anticancer activity
  • Dithiocarbamates
  • Drug delivery
  • Gold
  • Peptide transporters (PEPTs)
  • Peptidomimetics

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry


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