Titanocene–Gold Complexes Containing N‑Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro

We report on the synthesis, characterization,
and stability studies
of new titanocene complexes containing a methyl group and a carboxylate
ligand (mba = −OC­(O)-p-C6H4-S−) bound to gold­(I)–N-heterocyclic carbene
fragments through the thiolate group: [(η5-C5H5)2TiMe­(μ-mba)­Au­(NHC)]. The cytotoxicities
of the heterometallic compounds along with those of novel monometallic
gold–N-heterocyclic carbene precursors [(NHC)­Au­(mbaH)] have
been evaluated against renal, prostate, colon, and breast cancer cell
lines. The highest activity and selectivity and a synergistic effect
of the resulting heterometallic species was found for the prostate
and colon cancer cell lines. The colocalization of both titanium and
gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated
for the selected compound 5a, indicating the robustness
of the heterometallic compound in vitro. We describe here preliminary
mechanistic data involving studies on the interaction of selected
mono- and bimetallic compounds with plasmid (pBR322) used as a model
nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate
cancer cells. The heterometallic compounds, which are highly apoptotic,
exhibit strong antimigratory effects on the prostate cancer cell line
PC3.