# New N-Heterocyclic Carbene Gold and Platinum Complexes with 1,3-Dialkyl-4-anisyl-5-(4-chlorophenyl)imidazol-2-ylidene Ligands for the Treatment of Esophageal Adenocarcinoma

## TL;DR

Researchers developed new gold and platinum complexes with potential to treat esophageal adenocarcinoma by inhibiting cancer cell growth and inducing cell death.

## Contribution

New gold(I), gold(III), and platinum(II) complexes with N-heterocyclic carbene ligands show strong anticancer activity against esophageal adenocarcinoma.

## Key findings

- Cationic triphenylphosphino-NHC-gold(I) and bis-NHC-gold(I) complexes showed strong antiproliferative effects in EAC cell lines.
- Compounds induced caspase 3/7 activity and downregulated anti-apoptotic proteins in EAC cells.
- NHC-gold(I) complexes suppressed cyclin D1 and induced reactive oxygen species in EAC cells.

## Abstract

Encouraged by the promising anticancer activity of a iodidogold(I)-N-heterocyclic carbene (NHC) complex with a 1,3-diethyl-4-anisyl-5-(4-chlorophenyl)imidazol-2-ylidene ligand system, a series of new gold(I), gold(III) and platinum(II) complexes coordinated to this ligand system were designed, prepared, and characterized using NMR spectroscopy and mass spectrometry methods. A preliminary anticancer screening of the complexes using four esophageal adenocarcinoma (EAC) cell lines showed promising activities for the cationic triphenylphosphino-NHC-gold(I) and bis-NHC-gold(I) complexes, accompanied by strong antiproliferative, colony-, and spheroid-forming inhibitory effects. The compounds were relatively less toxic to the normal esophageal cell line Het-1A and the monocyte cell line THP-1. Moreover, these compounds induced caspase 3/7 activity and downregulated anti-apoptotic proteins (Bcl-XL, Bcl-2, and Mcl-1) in EAC cells. Further, the cell cycle promoter cyclin D1 was suppressed by these NHC-gold(I) complexes. Finally, we observed strong reactive oxygen species (ROS) induction in EAC cells with NHC-gold(I) complexes 8 and 11.