title: Titanocene-Gold Complexes Containing N-Heterocyclic Carbene Ligands Inhibit Growth of Prostate, Renal, and Colon Cancers in Vitro.
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 compound5a, 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.
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York 11210, United States; Chemistry and Biology Ph.D. Programs, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, New York 10016, United States.
authors.forename: Yiu Fung
authors.initials: YF
authors.lastname: Mui
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York , Brooklyn, New York 11210, United States.
authors.forename: Jacob
authors.initials: J
authors.lastname: Fernández-Gallardo
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York 11210, United States; Chemistry and Biology Ph.D. Programs, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, New York 10016, United States.
authors.forename: Benelita T
authors.initials: BT
authors.lastname: Elie
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York , Brooklyn, New York 11210, United States.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Gubran
authors.affiliation: Department of Chemistry, University of Sussex , Falmer, Brighton BN1 9QJ, U.K.
authors.forename: Irene
authors.initials: I
authors.lastname: Maluenda
authors.affiliation: Departamento de Química Inorgánica, Universidad de Valencia , Burjassot, Valencia 46100, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sanaú
authors.affiliation: Department of Chemistry, University of Sussex , Falmer, Brighton BN1 9QJ, U.K.
authors.forename: Oscar
authors.initials: O
authors.lastname: Navarro
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, Brooklyn, New York 11210, United States; Chemistry and Biology Ph.D. Programs, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, New York 10016, United States; Chemistry and Biology Ph.D. Programs, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, New York 10016, United States.
authors.forename: María
authors.initials: M
authors.lastname: Contel