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

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• 作者：Yiu Fung Mui ; Jacob Fernández-Gallardo ; Benelita T. Elie ; Ahmed Gubran ; Irene Maluenda ; Mercedes Sanaú ; Oscar Navarro ; Marı́a Contel
• 刊名：Organometallics
• 出版年：2016
• 出版时间：May 9, 2016
• 年：2016
• 卷：35
• 期：9
• 页码：1218-1227
• 全文大小：531K
• 年卷期：0
• ISSN：1520-6041

文摘

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.