Titanocene–gold complexes containing N-heterocyclic carbene ligands inhibit growth of prostate, renal, and colon cancers in vitro

Mui, Yiu Fung, Fernández-Gallardo, Jacob, Elie, Benelita T, Gubran, Ahmed, Maluenda, Irene, Sanaú, Mercedes, Navarro Fernandez, Oscar and Contel, Marı́a (2016) Titanocene–gold complexes containing N-heterocyclic carbene ligands inhibit growth of prostate, renal, and colon cancers in vitro. Organometallics, 35 (9). pp. 1218-1227. ISSN 0276-7333

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science > QD Chemistry > QD0146 Inorganic chemistry
Depositing User: John Spencer
Date Deposited: 06 Nov 2017 09:11
Last Modified: 06 Nov 2017 09:11
URI: http://sro.sussex.ac.uk/id/eprint/70901

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