12 research outputs found
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
Organometallic Titanocene–Gold Compounds as Potential Chemotherapeutics in Renal Cancer. Study of their Protein Kinase Inhibitory Properties
Early–late
transition metal TiAu<sub>2</sub> compounds [(η-C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>Ti{OC(O)CH<sub>2</sub>PPh<sub>2</sub>AuCl}<sub>2</sub>] (<b>3</b>) and new [(η-C<sub>5</sub>H<sub>5</sub>)<sub>2</sub>Ti{OC(O)-4-C<sub>6</sub>H<sub>4</sub>PPh<sub>2</sub>AuCl}<sub>2</sub>] (<b>5</b>) were evaluated
as potential anticancer agents <i>in vitro</i> against renal
and prostate cancer cell lines. The compounds were significantly more
effective than monometallic titanocene dichloride and gold(I) [{HOC(O)RPPh<sub>2</sub>}AuCl] (R = −CH<sub>2</sub>– <b>6</b>,
−4-C<sub>6</sub>H<sub>4</sub>– <b>7</b>) derivatives
in renal cancer cell lines, indicating a synergistic effect of the
resulting heterometallic species. The activity on renal cancer cell
lines (for <b>5</b> in the nanomolar range) was considerably
higher than that of cisplatin and highly active titanocene Y. Initial
mechanistic studies in Caki-1 cells <i>in vitro</i> coupled
with studies of their inhibitory properties on a panel of 35 kinases
of oncological interest indicate that these compounds inhibit protein
kinases of the AKT and MAPKAPK families with a higher selectivity
toward MAPKAPK3 (IC<sub>50</sub> <b>3</b> = 91 nM, IC<sub>50</sub> <b>5</b> = 117 nM). The selectivity of the compounds <i>in vitro</i> against renal cancer cell lines when compared to
a nontumorigenic human embryonic kidney cell line (HEK-293T) and the
favorable preliminary toxicity profile on C57black6 mice indicate
that these compounds (especially <b>5</b>) are excellent candidates
for further development as potential renal cancer chemotherapeutics
Study of the reactivity of carbosilane metallodendrimers containing n-donor monodentate or n,n-chelating ruthenium (ii) arene complexes with differents biomolecules
Медицинская биофизик
In Vitro and in Vivo Evaluation of Water-Soluble Iminophosphorane Ruthenium(II) Compounds. A Potential Chemotherapeutic Agent for Triple Negative Breast Cancer
A series
of organometallic ruthenium(II) complexes containing iminophosphorane
ligands have been synthesized and characterized. Cationic compounds
with chloride as counterion are soluble in water (70–100 mg/mL).
Most compounds (especially highly water-soluble <b>2</b>) are
more cytotoxic to a number of human cancer cell lines than cisplatin.
Initial mechanistic studies indicate that the cell death type for
these compounds is mainly through canonical or caspase-dependent apoptosis,
nondependent on p53, and that the compounds do not interact with DNA
or inhibit protease cathepsin B. In vivo experiments of <b>2</b> on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an
impressive tumor reduction (shrinkage) of 56% after 28 days of treatment
(14 doses of 5 mg/kg every other day) with low systemic toxicity.
Pharmacokinetic studies showed a quick absorption of <b>2</b> in plasma with preferential accumulation in the breast tumor tissues
when compared to kidney and liver, which may explain its high efficacy
in vivo