New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

Abstract

Inspired by the vascular-disrupting agent combretastatin A-4 and recently published anticancer active N-heterocyclic carbene (NHC) complexes of Au(I), a series of new iodidogold(I)–NHC complexes was synthesized and characterized. The iodidogold(I) complexes were synthesized by a route involving van Leusen imidazole formation and N-alkylation, followed by complexation with Ag2O, transmetalation with chloro(dimethylsulfide)gold(I) [Au(DMS)Cl], and anion exchange with KI. The target complexes were characterized by IR spectroscopy, 1H and 13C NMR spectroscopy, and mass spectrometry. The structure of 6c was validated via single-crystal X-ray diffraction. A preliminary anticancer screening of the complexes using two esophageal adenocarcinoma cell lines showed promising nanomolar activities for certain iodidogold(I) complexes accompanied with apoptosis induction, as well as c-Myc and cyclin D1 suppression in esophageal adenocarcinoma cells treated with the most promising derivative 6b.

Editorial for the Special Issue—“Recent Advances of Novel Pharmaceutical Designs for Anti-Cancer Therapies”

“…Complexes of other metals were also found to be highly active against tumors. Schleser et al prepared and evaluated a series of new iodidogold(I)-NHC (N-heterocyclic carbene) complexes in esophageal adenocarcinoma (EAC) cells [5]. The most active gold complexes of this study exhibited high antiproliferative activity, induced apoptosis, suppressed c-Myc and cyclin D1 expression, and inhibited EAC colony and spheroid formation.…”