Synthesis and in vitro antitumor activity of water soluble sulfonate- and ester-functionalized silver(I) N-heterocyclic carbene complexes

•[Na4(ImPrSO3)2]AgCl and [ImAcEt]AgCl have been synthesized and characterized.•[ImAcEt]AgCl X-ray analysis gave relevant structural information.•[Na4(ImPrSO3)2]AgCl showed a significant antiproliferative effect.•[Na4(ImPrSO3)2]AgCl efficiently inhibited thioredoxin reductase (TrxR).•[Na4(ImPrSO3)2]AgCl determined a cellular redox imbalance and apoptosis induction.

The novel N-heterocyclic carbene ligand precursor NaHImPrSO3 (sodium 3,3′-(1H-imidazole-3-ium-1,3-diyl)dipropane-1-sulfonate) and the related silver carbene complex [Na4(ImPrSO3)2]AgCl have been synthesized and characterized. Recrystallization of the analogous [ImAcEt]AgCl complex allowed the development of X-ray analysis which led to achieve relevant structural information concerning this silver(I) derivative. Both sulfonate- and ester-functionalized silver(I) N-heterocyclic carbenes (NHCs) were evaluated for their antiproliferative activities in a wide panel of human cancer cells. Complex [Na4(ImPrSO3)2]AgCl showed a significant in vitro antiproliferative activity that was correlated with its strong ability to inhibit thioredoxin reductase. The inhibition of this selenoenzyme determined an alteration of the cellular redox environment thus leading to the induction of the apoptotic cell death through the activation of the ASK-1 pathway.

Graphical abstractSilver carbene [Na4(ImPrSO3)2]AgCl and [ImAcEt]AgCl have been synthesized and characterized. [Na4(ImPrSO3)2]AgCl showed a significant antiproliferative activity, correlated with its ability to inhibit TrxR and to determine an alteration of the cellular redox state thus leading to apoptosis.Figure optionsDownload full-size imageDownload as PowerPoint slide