Novel NHC complexes of coinage metals: synthesis, cytotoxicity and solution behavior

N-Heterocyclic carbenes (NHCs) complexes represent new anticancer agents, normally with low toxicity profiles, and they provide a range of versatile structures for targeted biological applications [1]. In this field novel 1,3-symmetrically and 1,3-unsymmetrically substituted NHCs precursors have been synthesized (Figure 1) and used in the synthesis of multicharged metal-NHC complexes. In addition the novel NHC ligand precursor 1,4-bis(4-nitrobenzyl)-1H-1,2,4-triazol-4-ium bromide, [HTz(pNO2Bz)2]Br (Figure 1), has been synthesized and used in the synthesis of the corresponding metal complexes M[Tz(pNO2Bz)2]Br (M = Cu(I), Ag(I) or Au(I)). The cytotoxic properties of the NHCs complexes and of the corresponding uncoordinated ligands have been assessed in various human cancer cell lines, including cisplatin sensitive and resistant cells. Moreover, a detailed analysis of their molecular and cellular pharmacology has been performed in order to elucidate the role of the metallic core in determining the biological properties of this class of NHCs complexes. In particular, the ability of triazolium NHC compounds to hamper mammalian TrxR activity and proteasome functionality in human A431 cervical was investigated.