Synthesis and biological studies of silver N-heterocyclic carbene complexes derived from 4,5-diarylimidazole

Abstract

A novel class of silver N-heterocyclic carbene complexes ( 5a–f) were synthesized in high yield by reacting silver(I) oxide with 4,5-diarylimidazolium halides ( 4a–f). The complexes were characterized using NMR and IR spectroscopy. The structure was confirmed on the example of bromo[1,3-diethyl-4,5-bis(4-fluorophenyl)imidazol-2-ylidene]silver(I) ( 5c) by crystal structure analysis. The X-ray structure indicated a three-dimensional coordination polymer with a repeating unit consisting of a C carben-Ag 2-Br 2-C carben cluster. Pharmacological investigations revealed that all silver complexes possessed growth inhibitory effects against breast cancer (MCF-7 and MDA-MB-231) as well as colon carcinoma (HT-29) cells. The most active compound 5c was slightly less active against MCF-7 cells, more active against MDA-MB-231 cells and comparable active as cisplatin against HT-29 cells. Further pharmacological investigations were performed with selected compounds on estrogen receptor (ER) binding, DNA intercalation, cyclooxygenase (COX) inhibition and antibacterial activity. The complexes were only marginally active at the DNA, ER and the COX enzymes, so these targets can be excluded to be involved in the mode of action. However, the growth of bacteria was significantly inhibited by 5c and 5f and opens a new application of this complex type.