A gold(i) biscarbene complex with improved activity as a TrxR inhibitor and cytotoxic drug: comparative studies with different gold metallodrugs

Abstract

Gold complexes with N-heterocyclic carbene (NHC) ligands have been attracting major attention in medicinal inorganic chemistry based on their favorable antiproliferative effects and the structural versatility of the coordinated NHC ligands. Here we present a novel complex of the type (NHC)₂Au⁺, which represents a substantially improved and selective TrxR inhibitor compared to close structural analogues. The complex is highly stable in various solutions over 96 hours, however, comparative cellular uptake studies indicate metabolic transformations inside cells over time. A portfolio of other gold complexes (e.g. Auranofin) has been used as references in key biological assays, showing that the novel (NHC)₂Au⁺ complex exhibits substantially lower protein binding in combination with a strongly enhanced cytotoxic activity.