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 [Au₂Cu­(CCCH₂SC₅H₄N)₂L₂] (L = PTA, DAPTA, PPh₃, TPPTS) and [AuCu­(CCCH₂­SC₅H₄N)­(L)­(PPh₃)₂]­NO₃ (L = PTA, DAPTA) are reported. The X-ray crystal structure of [Au­(CC­CH₂SC₅H₄N)­(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>Rosa canina</i> Extracts Have Antiproliferative and Antioxidant Effects on Caco-2 Human Colon Cancer - Fig 5

<p><b>Cell-cycle analysis after treatment with two concentrations</b> (a: 125 and b: 1000 mg/L) of Fr 1: total extract (1), Fr 2: vit. C (2), Fr 3: neutral polyphenols (3) and Fr 4: acid polyphenols or flavonoids (4) from rosehip (<i>Rosa canina</i> L) after 72 h. In control (C), the cells are without treatment. Cell cycle and DNA fragmentation were determined by propidium iodide staining. Percentages of G₁, S and G₂-phase are shown when possible. Experiments were performed in triplicate.</p

Chemical formula, concentration and total antioxidant capacity of the different extract fractions.

<p>Chemical formula, concentration and total antioxidant capacity of the different extract fractions.</p

Summary of PD7 and TC7 colon cancer cells treated with two concentrations (a: 125 and b: 1000 mg/L) of rosehip (<i>Rosa canina</i> L) fractions after 72 h.

<p>In control, the cells are without treatment.</p

<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)₂P₂] were prepared from the reaction of <i>cis</i>-[MCl₂P₂] [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 [Pd₂Cl₂(<i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thionate)₂(PTA)₂], 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 (IC₅₀) 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)₂P₂] were prepared from the reaction of <i>cis</i>-[MCl₂P₂] [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 [Pd₂Cl₂(<i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thionate)₂(PTA)₂], 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 (IC₅₀) 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

Computational Modeling and Inelastic Neutron Scattering Contributions to the Study of Methyl-silica Xerogels: A Combined Theoretical and Experimental Analysis

In amorphous materials, such as xerogels, the properties are the key to most of their applications. Therefore, it is of great importance to get insight into the xerogel structure. In order to achieve a better understanding of structure formation in methyl-silica xerogels and thus be able to better influence the properties of these materials, we have chosen the molecular approach to model the hybrid–xerogel structure using the density functional theory. A theoretical cage model for hybrid xerogels was performed from the PBEPBE/6-31G­(d,p) method. The model could explain the presence of ordered domains in the structure. A comprehensive listing of all IR and ²⁹Si NMR assignments is provided. The effects in the structure of the organic functional groups incorporated on the host structure network are investigated using inelastic neutron scattering spectroscopy (INS). The combination of experiments and modeling permitted an analysis of the INS studies, including unique INS assignments, contributing to the understanding of the skeletal SiO₂ network of silica xerogels and so to obtain information about the structure of this material