The team is involved in the design and development of new molecules with anticancer activity based on the original properties of certain metals and their complexes. The team introduced a whole range of molecules coined ferrocifens (fig. 1) initially designed from the SERM tamoxifen (TAM) and its active metabolite hydroxy-tamoxifen (OH-TAM). Conversely to OH-TAM, some of these molecules display an antiproliferative activity on both ER(+) and ER(-) breast cancer cell lines.
The original biological activity of these molecules is linked to the low redox potential of ferrocene (0.4 V) and the presence of a Fc-ene-phenol motif in trans stereoconfiguration. For instance, chemical, electrochemical or enzymatic (HRP or liver microsomes) oxidation of Fc-OHTAM afforded one or several metabolites among which a quinone methide (QM, fig. 2) that is able to inhibit the selenoenzyme thioredoxin reductase both in vitro and in cellulo.
In vivo studies were carried out on glioblastoma tumors implanted in rats. Partial to full regression of the tumor size was observed after iv injection of Fc-diOH formulated in lipid nanocapsules.
G. Jaouen, A. Vessières, S. Top. Ferrocifen type anticancer drugs. Chem. Soc. Rev. 2015, 44, 8802-8817. DOI : 10.1039/c5cs00486a