N-Heterocyclic Carbene (NHC) Gold(I) complexes targeting the Thioredoxin System: a mass spectrometry study

Thioredoxin (Trx) and Thioredoxin Reductase (TrxR) enzymes are essential constituents of the Trx system involved in the cellular redox regulation network. This mitochondrial apparatus, in recent years, has been recognized as an important modulator of tumor growth; hence specific inhibitors are developed to target TrxR/Trx for cancer treatment[1]. Trx and TrxR redox active sites are characterized by the presence, respectively, of two cysteine (WCGPCK) at the N-terminus and by a selenol thiol motif (GCUG, where U=SeCys) at the C-terminus. Both Cys and SeCys are Lewis soft base therefore Au(I) based compounds show high affinity for these targets. In this context, while TrxR has been largely explored as target of cytotoxic gold complexes [2], Trx has been neglected. Here, we selected and synthesized two (NHC)2-gold(I) complexes (Figure 1), able to cross mitochondrial membrane, and investigated by mass spectrometry their interaction with Trx in comparison with the Au(I) drug auranofin.