Heterobimetallic aluminate derivatives with bulky phenoxide ligands: a catalyst for selective vinyl polymerization.

New aluminium-alkali metal heterometallic compounds using the bulky ligand OAr = 2,6-bis(diphenylmethyl)-4-tert-butylphenoxide have been synthesized and characterized. The species obtained, [MAlMe3(OAr)] (M = Li(2a), Na(2b), K(2c)) and [MAlMe2(OAr)2] (M = Li(3a), Na(3b), K(3c)), include some of the few heterobimetallic examples of aluminate complexes with O-donor ligands described so far. Their activity in polymerization towards a difunctional monomer, such as Glycidyl Methacrylate (GMA), was evaluated. The compounds were revealed to be able to polymerize the acrylate groups via vinyl polymerization. Interestingly, the homometallic counterparts [AlXMe(OAr)] (X = Cl, Me), previously described by us, are very active in ROP processes of GMA. The combined polymerization process using both catalysts has also been explored to obtain a polymeric material with an exciting macromolecular architecture.

Thioredoxin-80 is a product of alpha-secretase cleavage that inhibits amyloid-beta aggregation and is decreased in Alzheimer's disease brain.

Thioredoxin-1 (Trx1) is an endogenous dithiol reductant and antioxidant that was shown to be decreased in Alzheimer's disease (AD) neurons. A truncated form of Trx1, thioredoxin 80 (Trx80), was reported to be secreted from monocytes having cytokine activity. Here, we show that Trx80 is present in human brain in an aggregated form. Trx80 localizes mainly to neurons and is dramatically decreased in AD brains. Trx80 levels in cerebrospinal fluid (CSF) correlate with those of the classical AD biomarkers amyloid-ß (Aß) 1-42 and total tau. Moreover, Trx80 measurements in CSF discriminate between patients with stable mild cognitive impairment, prodomal AD and mild AD. We report that ADAM10 and 17, two α-secretases processing the Aß precursor protein, are responsible for Trx80 generation. In contrast to the periphery, Trx80 has no pro-inflammatory effects in glia, either by itself or in combination with Aß or apolipoprotein E. Instead, Trx80 inhibits Aß(1-42) aggregation and protects against its toxicity. Thus, a reduction in Trx80 production would result in increased Aß polymerization and enhanced neuronal vulnerability. Our data suggest that a deficit in Trx80 could participate in AD pathogenesis.

Crystallization and preliminary crystallographic analysis of the measles virus hemagglutinin in complex with the CD46 receptor.

The measles virus (MV) hemagglutinin (MV-H) mediates the attachment of MV particles to cell-surface receptors for entry into host cells. MV uses two receptors for attachment to host cells: the complement-control protein CD46 and the signalling lymphocyte activation molecule (SLAM). The MV-H glycoprotein from an Edmonston MV variant and the MV-binding fragment of the CD46 receptor were overproduced in mammalian cells and used to crystallize an MV-H-CD46 complex. Well diffracting crystals containing two complexes in the asymmetric unit were obtained and the structure of the complex was solved by the molecular-replacement method.

Antiobesity designed multiple ligands: Synthesis of pyrazole fatty acid amides and evaluation as hypophagic agents.

Searching for new antiobesity agents, a new series of fatty acid amide derivatives of 1,5-diarylpyrazole have been synthesized as dual peroxisome proliferator activated receptor alpha (PPARalpha)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARalpha activators and as cannabinoids in two tests of the mouse tetrad. In vivo, food intake studies have been performed with all the compounds. No significant cannabinoid activity has been found but some compounds behaved as potent PPARalpha activators. Several compounds showed anorexigenic properties reducing food intake in rats.

Evaluation of antiproliferative activities and apoptosis induction caused by copper(II)-benzothiazolesulfonamide complexes in Jurkat T lymphocytes and Caco-2 cells.

Two copper(II) complexes with a benzothiazolesulfonamide ligand, [Cu(L)2(py)2] (1) and [Cu(en)2(L)2] (2) [HL is N-2-(4-methylbenzothiazole)toluenesulfonamide, py is pyridine, en is ethylenediamine], were prepared and then characterized with the aid of X-ray crystallography and spectroscopy. Whereas the copper(II) ion in 1 presents a square-planar geometry, in 2 it has a distorted octahedral environment. In addition, although the ligand is monodentate in both complexes, it exhibits different coordination behavior in each, interacting through the benzothiazole nitrogen atom in 1 and through the sulfonamide nitrogen atom in 2. The propensity for binding of 1 and 2 to calf thymus DNA was studied by thermal denaturation, viscosimetry, and cyclic voltammetry. The ability of the complexes to cleave DNA was studied in vitro through ascorbate activation and was tested by monitoring the expression of the yEGFP gene containing the RAD54 reporter. Moreover, their antiproliferative activity was verified in two cellular models: yeast and human tumor cells in culture. While 1 was found to be the more active cleaving agent in vitro, 2 showed a higher propensity for inflicting DNA damage at the cellular level. The biological studies carried out with human tumor cells, namely, colon adenocarcinoma Caco-2 cells (HTB-37) and leukemia Jurkat T lymphocytes (TIB-152), confirmed that both compounds inhibit the growth of these cell lines, although 2 is more effective. This difference is associated with the latter compound's greater ability to induce cell death by apoptosis.