Halo and Pseudohalo Gold(I)-NHC Complexes Derived from 4,5-Diarylimidazoles with Excellent and Anticancer Activities Against HCC.

A series of halo and pseudohalo gold(I)-NHC complexes (NHC-Au-X) (X = Cl, Br, I, NCO, and OAc) derived from 4,5-diarylimidazoles were synthesized, structurally characterized, and analyzed for their biological activities. The most active complex was iodo(1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene)gold(I) (), which was at least 2-fold more cytotoxic than cisplatin and auranofin against hepatocellular carcinoma (HCC) cells. studies indicated that complex exhibited a considerably higher anticancer efficacy (IRT = 75.7%) than cisplatin (IRT = 44.4%) in a HepG2 xenograft mouse model and ameliorated liver injury caused by CCl in chronic HCC. Further studies revealed that complex can inhibit the expression of the thioredoxin reductase (TrxR) both and , block the HepG2 cells in the G2/M phase, induce reactive oxygen species (ROS) production, damage mitochondrial membrane potential (MMP), and promote HepG2 cell apoptosis.