NHC Gold Halide Complexes Derived from 4,5-Diarylimidazoles: Synthesis, Structural Analysis, and Pharmacological Investigations as Potential Antitumor Agents

Abstract

A series of novel neutral NHC gold halide complexes derived from 4,5-diarylimidazoles were synthesized, characterized, and analyzed for biological effects. High growth inhibitory effects in MCF-7 and MDA-MB 231 breast cancer as well as HT-29 colon cancer cell lines depended on the presence of the C4,C5-standing aromatic rings. Methoxy groups at these rings did not change the growth inhibitory properties, while F-substituents in the ortho-position (5d) increased the activity in MCF-7 and MDA-MB 231 cells. The substituents at the nitrogen atoms and the oxidation state of the metal play a subordinate role. The most active bromo[1,3-diethyl-4,5-bis(2-fluorophenyl)-1,3-dihydro-2H-imidazol-2-ylidene]gold(I) (5d) was distinctly more active than cisplatin. All complexes caused thioredoxin reductase (TrxR) inhibition (EC50=374-1505 nM) distinctly lower than auranofin (EC50=18.6 nM) excluding this enzyme as main target. Because of the low nuclear content, a participation of DNA interaction on the mode of action is very unlikely. The missing ER binding and the missing correlation of growth inhibition and inactivation of COX enzymes exclude these targets, too.

Silver(I), Gold(I) and Gold(III)-N-Heterocyclic carbene complexes of naphthyl substituted annelated ligand: Synthesis, structure and cytotoxicity

“…As Au(III) and Pt(II) are isoelectronic and they have square planer geometry one expected it would be nice choice of Au(III) as alternative as many cases cisplatin is resistive towards a series cancer cell lines. Guest's group has shown that Au(III)eNHC complexes of 4,5-diarylimidazolidene are very potent against MCF-7, HT-29, HCT-116 and HEP-G2 Cells [42], But it is also observed in many cases Au(III)eNHC are less potent than corresponding Au(I)e NHC complexes as Au(III) finally reduced to Au(I) under physiological condition [13]. Present Au(III) compound, 4 is lees potent than reported Au(III)eNHC by our group; probably bulky naphthyl group prohibit to enter into the cell which is the reason of lower potency.…”

Synthesis and electronic properties of N-heterocyclic carbene-containing conducting polymers with coinage metals

“…[13][14][15] NHCs have also been attractive key components in the field of medicinal chemistry. 16,17 Notably, NHCs are well known for stabilizing ligands of virtually every transition metal with strong electron donation from nitrogen atoms to the carbene-metal bond. 18,19 These interesting compounds predominantly enrich the organometallic chemistry as the ligands for stabilizing the metal center.…”

Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation

“…Therefore the development of more stable gold complexes with fine tuning of their ligands is of particular interest [11]. With the NHC ligands showing donor properties similar to those of phosphines, the ease of systemic modifications of the NHC substituents has made them attractive ligands for the development of gold complexes as potential apoptotic agents against cancer cells [12]. It may be mentioned that cancer cell death through apoptosis is a desired goal.…”