4 research outputs found
Novel Gold(I) Thiolate Derivatives Synergistic with 5‑Fluorouracil as Potential Selective Anticancer Agents in Colon Cancer
New gold(I) thiolate
complexes have been synthesized and characterized, and their physicochemical
properties and anticancer activity have been tested. The coordination
of PTA derivatives provides optimal hydrophilicity/lipophilicity properties
to the complexes, which present high solution stability. Moreover,
the complexes show a high anticancer activity against Caco-2 cells,
comparable to that of auranofin, and a very low cytotoxic activity
against enterocyte-like differentiated cells. Their activity has been
shown to produce cell death by apoptosis and arrest of the cell cycle
because of interaction with the reductase enzymes and consequent reactive
oxygen species production. Some of these new complexes are also able
to decrease the necessary dose of 5-fluorouracil, a drug used for
the treatment of colon cancer, by a synergistic mechanism
<i>S</i>‑Propargylthiopyridine Phosphane Derivatives As Anticancer Agents: Characterization and Antitumor Activity
<i>S</i>-Propargylthiopyridine
phosphane gold(I) derivatives with
the water-soluble phosphanes PTA (1,3,5-triaza-7-phosphaadamantane),
DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), and
TPPTS (sodium triphenylphosphane trisulfonate) are described and used
as metalloligands by coordination to copper(I). New heteronuclear
gold(I) and copper(I) complexes of the type [Au<sub>2</sub>Cu(CCCH<sub>2</sub>SC<sub>5</sub>H<sub>4</sub>N)<sub>2</sub>L<sub>2</sub>] (L
= PTA, DAPTA, PPh<sub>3</sub>, TPPTS) and [AuCu(CCCH<sub>2</sub>SC<sub>5</sub>H<sub>4</sub>N)(L)(PPh<sub>3</sub>)<sub>2</sub>]NO<sub>3</sub> (L = PTA, DAPTA) are reported. The X-ray crystal
structure of [Au(CCCH<sub>2</sub>SC<sub>5</sub>H<sub>4</sub>N)(PTA)] (<b>1</b>), which confirms the coordination
of the metallic center to the alkyne unit, displays a zigzag polymeric
chain with short gold–gold contacts of 3.2680(16) Å. Strong
antiproliferative effects are found for most of the new complexes
in human colon cancer cell lines (Caco-2, PD7, and TC7 clones), with
these effects being more pronounced than for the reference drugs cisplatin
and auranofin, especially for the heterodimetallic derivatives, which
are markedly more active than the corresponding mononuclear precursors.
Apoptosis-induced cell death is found for all compounds, as shown
by an annexin-V/propidium iodide double-staining assay
<i>trans</i>-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines
A series
of PTA and DAPTA platinum(II) and palladium(II) thionate
complexes of the type <i>trans</i>-[M(SN)<sub>2</sub>P<sub>2</sub>] were prepared from the reaction of <i>cis</i>-[MCl<sub>2</sub>P<sub>2</sub>] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane),
DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with
the <i>in situ</i> generated sodium salts of the heterocyclic
thiones <i>S</i>-<i>m</i>-methylpyrimidine-2-thione, <i>S</i>-4,6-dimethylpyrimidine-2-thione, <i>S</i>-4,6-dihydroxypyrimidine-2-thione,
benzothiazole-2-thione, benzoxazole-2-thione, <i>S</i>-1,3,4,-thiadiazole-2-thione, <i>S</i>-4,5-<i>H</i>-thiazolan-2-thione, and <i>S</i>-pyrimidine-4(1<i>H</i>)-one-2-thione. The X-ray
structures of six of the compounds confirm the <i>trans</i> disposition and, only in the case of [Pd<sub>2</sub>Cl<sub>2</sub>(<i>S</i>-pyrimidine-4(1<i>H</i>)-one-2-thionate)<sub>2</sub>(PTA)<sub>2</sub>], a dinuclear structure with a Pd–Pd
distance of 3.0265(14)Å was observed. <i>In vitro</i> cytotoxicities against human ovarian cancer cell lines A2780 and
A2780cisR were evaluated for ten complexes showing a high inhibition
of cellular growth with a comparable inhibitory potency (IC<sub>50</sub>) against A2780 cells to that of cisplatin. Notably, the compounds
also show significant (up to 7-fold higher) activity in cisplatin-resistant
A2780cisR cell lines
<i>trans</i>-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines
A series
of PTA and DAPTA platinum(II) and palladium(II) thionate
complexes of the type <i>trans</i>-[M(SN)<sub>2</sub>P<sub>2</sub>] were prepared from the reaction of <i>cis</i>-[MCl<sub>2</sub>P<sub>2</sub>] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane),
DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane)] with
the <i>in situ</i> generated sodium salts of the heterocyclic
thiones <i>S</i>-<i>m</i>-methylpyrimidine-2-thione, <i>S</i>-4,6-dimethylpyrimidine-2-thione, <i>S</i>-4,6-dihydroxypyrimidine-2-thione,
benzothiazole-2-thione, benzoxazole-2-thione, <i>S</i>-1,3,4,-thiadiazole-2-thione, <i>S</i>-4,5-<i>H</i>-thiazolan-2-thione, and <i>S</i>-pyrimidine-4(1<i>H</i>)-one-2-thione. The X-ray
structures of six of the compounds confirm the <i>trans</i> disposition and, only in the case of [Pd<sub>2</sub>Cl<sub>2</sub>(<i>S</i>-pyrimidine-4(1<i>H</i>)-one-2-thionate)<sub>2</sub>(PTA)<sub>2</sub>], a dinuclear structure with a Pd–Pd
distance of 3.0265(14)Å was observed. <i>In vitro</i> cytotoxicities against human ovarian cancer cell lines A2780 and
A2780cisR were evaluated for ten complexes showing a high inhibition
of cellular growth with a comparable inhibitory potency (IC<sub>50</sub>) against A2780 cells to that of cisplatin. Notably, the compounds
also show significant (up to 7-fold higher) activity in cisplatin-resistant
A2780cisR cell lines