1 research outputs found
From Catalysis to Cancer: Toward StructureâActivity Relationships for Benzimidazol-2-ylidene-Derived <i>N</i>âHeterocyclic-Carbene Complexes as Anticancer Agents
The promise of the metalÂ(arene) structure
as an anticancer pharmacophore has prompted intensive exploration
of this chemical space. While <i>N</i>-heterocyclic carbene
(NHC) ligands are widely used in catalysis, they have only recently
been considered in metal complexes for medicinal applications. Surprisingly,
a comparatively small number of studies have been reported in which
the NHC ligand was coordinated to the Ru<sup>II</sup>(arene) pharmacophore
and even less with an Os<sup>II</sup>(arene) pharmacophore. Here,
we present a systematic study in which we compared symmetrically substituted
methyl and benzyl derivatives with the nonsymmetric methyl/benzyl
analogues. Through variation of the metal center and the halido ligands,
an in-depth study was conducted on ligand exchange properties of these
complexes and their biomolecule binding, noting in particular the
stability of the MâC<sub>NHC</sub> bond. In addition, we demonstrated
the ability of the complexes to inhibit the selenoenzyme thioredoxin
reductase (TrxR), suggested as an important target for anticancer
metalâNHC complexes, and their cytotoxicity in human tumor
cells. It was found that the most potent TrxR inhibitor diiodidoÂ(1,3-dibenzylbenzimidazol-2-ylidene)Â(η<sup>6</sup>-p-cymene)ÂrutheniumÂ(II) <b>1b</b><sup><b>I</b></sup> was also the most cytotoxic compound of the series, with the
antiproliferative effects in general in the low to middle micromolar
range. However, since there was no clear correlation between TrxR
inhibition and antiproliferative potency across the compounds, TrxR
inhibition is unlikely to be the main mode of action for the compound
type and other target interactions must be considered in future