Among the twenty gold-based compounds Benoit Bertrand synthesized, two of them presented interesting selective toxicity for cancer cells compared to healthy cells and tissues and deserve further investigations as potential anticancer drugs.
Currently, platinum-based compounds are present in the majority of the chemotherapeutic cocktails. However, despite their clinical success, platinum-based drugs present several limitations including numerous and severe side effects. A strategy envisaged to overcome these limitations is the replacement of platinum by other transition metals. Among the different metals tested over the years, gold compounds have been shown to be promising as they can overcome resistance to cisplatin due to their different modes of action.
In his thesis, Bertrand presents the synthesis of different types of gold-based complexes including gold(I)-N-heterocyclic carbenes (NHC), (C^N) cyclometalated gold(III) complexes as well as heterobimetallic complexes bearing a gold(I)-NHC moiety. These compounds show higher stability in a physiological environment compared to classical platinum complexes The different compounds have been tested in panels of human cancer cell lines and a model of human healthy kidney cells. Moreover, “bifunctional” lansoprazole-based gold(I) complexes were also evaluated for their biological properties in vitro. On selected compounds we also performed mechanistic studies to try to elucidate their possible mechanisms of action. Specifically, we investigated two possible enzyme targets: thioredoxin reductase and poly(ADP-ribose) polymerase 1, as well as DNA G-quadruplexes. The cellular uptake of some fluorescent compounds was also studied using confocal microscopy techniques. In a few cases, we also assessed their toxicity ex vivo in rat healthy tissues using the precision-cut tissue slices technique.
Mr B.C. (Benoit) Bertrand
January 16, 2015
prof. dr. G.M.M. (Geny) Groothuis, P. Le Gendre
After a decade of preparations, it’s finally time: on the evening of 20 September the German icebreaker Polarstern departs from the Norwegian port of Tromsø. Escorted by the Russian icebreaker Akademik Fedorov, she will set sail for the Central Arctic...
Noorderlicht and the University of Groningen (RUG) continue their collaboration in the ‘Imagining Science’ series. Each year they commission a photographer to depict a scientific research field in relation to the Noorderlicht festival-theme of the year...
Banks with a high sustainability score have a lower default risk. In addition, the most sustainable banks help to reduce the systemic risk of the financial system as a whole. These are the conclusions of Bert Scholtens, Professor of Sustainable Banking...