Gold(I) complexes with NHC ligands functionalized with sulfoxide groups: Design, synthesis, in vitro studies and insights into the mechanism of action as anticancer drugs

Mononuclear silver(I) complexes of the type [AgBr(NHC)] (NHC=N-heterocyclic carbene) were prepared by reaction of the imidazolium salt NHC·HBr with Ag2O. The corresponding gold(I) complexes [AuCl(NHC)] were isolated by transmetalation reaction from the silver complex to the [AuCl(SMe2)] precursor. The employed NHC ligands are characterized by benzyl and CH2CH2S(O)R (R = Ph or t-Bu) groups as nitrogen wingtip substituents. The antiproliferative activity of the Ag(I) and Au(I) complexes on a panel of different human cancer cell lines is reported. The results show that gold(I) complexes are more active than the analogous silver(I) ones, and between the two gold(I) complexes, the one with R = Ph displays the best results, with IC50 values ranging from 5.4 to 30.6 μM. Mechanistic studies confirm the ability of the reported complexes to hamper Thioredoxin Reductase (TrxR) activity and cellular redox homeostasis, thus leading to oxidative stress induction.