Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: Synthesis and biological properties

Benoiît Bertrand, Loic Stefan, Marc Pirrotta, David Monchaud, Ewen Bodio, Philippe Richard, Pierre Le Gendre, Elena Warmerdam, Marina H. De Jager, Geny M.M. Groothuis, Michel Picquet, Angela Casini

Research output: Contribution to journalArticlepeer-review

191 Scopus citations


A new series of gold(I) N-heterocyclic carbene (NHC) complexes based on xanthine ligands have been synthesized and characterized by mass spectrometry, NMR, and X-ray diffraction. The compounds have been tested for their antiproliferative properties in human cancer cells and nontumorigenic cells in vitro, as well as for their toxicity in healthy tissues ex vivo. The bis-carbene complex [Au(caffein-2-ylidene)2][BF4] (complex 4) appeared to be selective for human ovarian cancer cell lines and poorly toxic in healthy organs. To gain preliminary insights into their actual mechanism of action, two biologically relevant in cellulo targets were studied, namely, DNA (more precisely a higher-order DNA structure termed G-quadruplex DNA that plays key roles in oncogenetic regulation) and a pivotal enzyme of the DNA damage response (DDR) machinery (poly-(adenosine diphosphate (ADP)-ribose) polymerase 1 (PARP-1), strongly involved in the cancer resistance mechanism). Our results indicate that complex 4 acts as an efficient and selective G-quadruplex ligand while being a modest PARP-1 inhibitor (i.e., poor DDR impairing agent) and thus provide preliminary insights into the molecular mechanism that underlies its antiproliferative behavior.

Original languageEnglish
Pages (from-to)2296-2303
Number of pages8
JournalInorganic Chemistry
Issue number4
StatePublished - 17 Feb 2014
Externally publishedYes


Dive into the research topics of 'Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: Synthesis and biological properties'. Together they form a unique fingerprint.

Cite this