JBIC Journal of Biological Inorganic Chemistry

, Volume 14, Issue 7, pp 1139–1149 | Cite as

Chemistry, antiproliferative properties, tumor selectivity, and molecular mechanisms of novel gold(III) compounds for cancer treatment: a systematic study

  • Angela CasiniEmail author
  • Gerhard Kelter
  • Chiara Gabbiani
  • Maria Agostina Cinellu
  • Giovanni Minghetti
  • Dolores Fregona
  • Heinz-Herbert Fiebig
  • Luigi MessoriEmail author
Original Paper


The antiproliferative properties of a group of 13 structurally diverse gold(III) compounds, including six mononuclear gold(III) complexes, five dinuclear oxo-bridged gold(III) complexes, and two organogold(III) compounds, toward several human tumor cell lines were evaluated in vitro using a systematic screening strategy. Initially all compounds were tested against a panel of 12 human tumor cell lines, and the best performers were tested against a larger 36-cell-line panel. Very pronounced antiproliferative properties were highlighted in most cases, with cytotoxic potencies commonly falling in the low micromolar—and even nanomolar—range. Overall, good-to-excellent tumor selectivity was established for at least seven compounds, making them particularly attractive for further pharmacological evaluation. Compare analysis suggested that the observed antiproliferative effects are caused by a variety of molecular mechanisms, in most cases “DNA-independent,” and completely different from those of platinum drugs. Remarkably, some new biomolecular systems such as histone deacetylase, protein kinase C/staurosporine, mammalian target of rapamycin/rapamycin, and cyclin-dependent kinases were proposed for the first time as likely biochemical targets for the gold(III) species investigated. The results conclusively qualify gold(III) compounds as a promising class of cytotoxic agents, of outstanding interest for cancer treatment, while providing initial insight into their modes of action.

Graphical Abstract

A series of gold(III) compounds showed cytotoxic properties and tumor selectivity toward a panel of cancer cell lines. Compare analysis provided insight into their possible mechanisms of action.


Anticancer drug Structure–function relationship 



We gratefully acknowledge support from Ente Cassa di Risparmio di Firenze and from the Italian Consortium C.I.R.C.M.S.B. C.G. wishes to thank AIRC for providing her with a Research Fellowship. A.C. thanks the Swiss National Science Foundation for financial support (project number PZ00P2_121933).

Supplementary material

775_2009_558_MOESM1_ESM.pdf (1.9 mb)
Supplementary material (PDF 1987 kb)


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Copyright information

© SBIC 2009

Authors and Affiliations

  • Angela Casini
    • 1
    Email author
  • Gerhard Kelter
    • 2
  • Chiara Gabbiani
    • 3
  • Maria Agostina Cinellu
    • 4
  • Giovanni Minghetti
    • 4
  • Dolores Fregona
    • 5
  • Heinz-Herbert Fiebig
    • 2
  • Luigi Messori
    • 3
    Email author
  1. 1.Laboratory of Organometallic and Medicinal Chemistry, Institut des Sciences et Ingénierie ChimiquesEcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  2. 2.Institute for Experimental OncologyOncotest GmbHFreiburgGermany
  3. 3.Laboratory of Metals in Medicine, Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly
  4. 4.Department of ChemistryUniversity of SassariSassariItaly
  5. 5.Department of Chemical SciencesUniversity of PaduaPaduaItaly

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