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Gold-based complexes: synthesis and evaluation as anticancer agents

08 January 2015

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.

PhD ceremony:

Mr B.C. (Benoit) Bertrand

When:

January 16, 2015

Start:

14:30

Promotors:

prof. dr. G.M.M. (Geny) Groothuis, P. Le Gendre

Last modified:08 January 2015 10.46 a.m.
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