Halo and Pseudohalo Gold(I)–NHC Complexes Derived from 4,5-Diarylimidazoles with Excellent In Vitro and In Vivo 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) (6), which was at least 2-fold more cytotoxic than cisplatin and auranofin against hepatocellular carcinoma (HCC) cells. In vivo studies indicated that complex 6 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 CCl4 in chronic HCC. Further studies revealed that complex 6 can inhibit the expression of the thioredoxin reductase (TrxR) both in vitro and in vivo, 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.