Comparative in Vitro Evaluation of N-Heterocyclic Carbene Gold(I) Complexes of the Benzimidazolylidene Type

Abstract

Gold(I) complexes with a 1,3-diethylbenzimidazol-2-ylidene N-heterocyclic carbene (NHC) ligand of the type NHC-Au-L (L=-Cl, -NHC, or -PPh3) were comparatively evaluated as thioredoxin reductase (TrxR) inhibitors and antimitochondrial anticancer agents. Different effects were noted in various biochemical assays (e.g., inhibition of TrxR, cellular and mitochondrial uptake, or effects on mitochondrial membrane potential), and this was related to properties of the complexes such as bond dissociation energies and overall charge. Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.

BIAN N-Heterocyclic Gold Carbene Complexes induced cytotoxicity in human cancer cells via upregulating oxidative stress

“…The reactivity of a carbene is influenced by the nature of the substituents attached to the carbene carbon atom (Bourissou et al, 2000). The N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and a few of them have been reported as potential chemotherapeutic agents (Hindi et al, 2009;Teyssot et al, 2009;Gautier and (Hickey et al, 2008a;Rubbiani et al, 2011). The anti-mitochondrial properties of cationic, linear Au(I) N-heterocyclic carbene complexes have also been reported in another study (Baker et al, 2006).…”

Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents

“…Indeed, Rubbiani et al synthesized three NHC gold(I) complexes of the 1,3-benzimidazol-2-ylidene type ( Fig. 1) with different ligands (Cl, NHC, and PPh 3 , respectively) [27]. As the chlorido and phosphane derivatives are more prone to ligand substitution reactions, they are stronger inhibitors of the seleno-enzyme thioredoxin reductase (TrxR) than the cationic biscarbene.…”

Synthesis and Cytotoxicity of Dinuclear Silver(I)-N-Heterocyclic Carbene Complexes

“…Except transition metals, the organometallic compounds based on coinage metals (Ag, Au, Cu) have now attracted the researchers for medicinal applications [4,5]. Recently, Au(I)-NHC complexes have been tested against HCT 116 cell line (Chart 2), showed significant in vitro anticancer results [6]. However, according to the published studies, Ag(I)-N-Heterocyclic Carbene (NHC) complexes have been rarely studied against this specific cancer.…”