Gold(i) and gold(iii) carbene complexes from the marine betaine norzooanemonin: inhibition of thioredoxin reductase, antiproliferative and antimicrobial activity†

Abstract

The natural marine betaine norzooanemonin (1,3-dimethylimidazolim-4-carboxylate) and its methyl and ethyl esters were used as ligand precursors to prepare a systematic series (12 members) of neutral monocarbene gold(I/III) and cationic dicarbene gold(I/III) complexes. The complexes were evaluated as inhibitors of bacterial thioredoxin reductase and for their antiproliferative and antimicrobial activities. While gold complexes with the parent norzooanemonin scaffold resulted in overall poor performance, the more lipophilic esters proved to be highly bioactive agents, related to their higher cellular uptake. The monocarbene gold(I/III) complexes showed significant potency as inhibitors of bacterial thioredoxin reductase. In most assays, the efficacy of both gold(I) and gold(III) analogues was found to be comparable. The cytotoxicity of dicarbene gold(I/III) complexes against cancer cells was strong, in some cases exceeding that of the standard reference auranofin.