Novel antiproliferative biphenyl nicotinamide: NMR metabolomic study of its effect on the MCF-7 cell in comparison with cisplatin and vinblastine

A 1H-NMR-based metabolomic study was performed on MCF-7 cell lines treated with a novel nicotinamide derivative (DT-8) in comparison with two drugs characterized by a well-established mechanism of action, namely the DNA-metalating drug cisplatin (cis-diamminedichloridoplatinum(II), CDDP) and the antimitotic drug vinblastine (vinblastine, VIN). The effects of the three compounds, each one at the concentration corresponding to the IC50 value, were investigated, with respect to the controls (K), by the 1H-NMR of cells lysates and multivariate analysis (MVA) of the spectroscopic data. Relevant differences were found in the metabolic profiles of the different treatments with respect to the controls. A large overlap of the metabolic profiles in DT-8 vs. K and VIN vs. K suggests a similar biological response and mechanism of action, significantly diverse with respect to CDDP. On the other hand, DT8 seems to act by disorganizing the mitotic spindle and ultimately blocking the cell division, through a mechanism implying methionine depletion and/or S-adenosylmethionine (SAM) limitation

The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor.

Signaling pathways have a key role in driving the uncontrolled development of familial adenomatous polyposis (FAP)- associated and sporadic desmoid tumors (DTs). The relationship between the Wnt/b-catenin signaling pathway and DTs has been extensively studied, but no reliable biomarkers able to detect their histological subtype have been identified for the accurate diagnosis. In this study we studied the differences in miRNA expression between sporadic (20 patients) and FAP-associated DTs (7 patients) using microarray confirmed by quantitative PCR (qPCR). The analysis showed 19 dysregulated miRNAs. Among them miR-133b levels were significantly lower in FAP-associated DT than in sporadic DT. Therefore, two mRNAs, associated to miR-133b and β-catenin expression, the SIRT1 and ELAVL1were analyzed. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated DT than in sporadic DT, whereas no differences in ELAVL1 expression was observed between these two DT types. In addition, a negative correlation was observed between miR-133b and SIRT1 in FAP-associated DTs, but not in sporadic DTs. The miR-133b-SIRT1-β-catenin axis may represent a novel mechanism underlying progression of FAP-associated D

Diammonium biphenyl-4,4′-disulfonate

In the title salt, 2NH4 +·C12H8O6S2 2−, the dianion has crystallographic inversion symmetry. A three-dimensional framework is formed from primary hydrogen-bonded sheet structures comprising ammonium N—H⋯Osulfonate inter­actions and is linked peripherally through the biphenyl residues of the anions. This open framework has 43 Å3 solvent-accessible voids

Circuit QED scheme for realization of the Lipkin-Meshkov-Glick model

We propose a scheme in which the Lipkin-Meshkov-Glick model is realized within a circuit QED system. An array of N superconducting qubits interacts with a driven cavity mode. In the dispersive regime, the cavity mode is adiabatically eliminated generating an effective model for the qubits alone. The characteristic long-range order of the Lipkin-Meshkov-Glick model is here mediated by the cavity field. For a closed qubit system, the inherent second order phase transition of the qubits is reflected in the intensity of the output cavity field. In the broken symmetry phase, the many-body ground state is highly entangled. Relaxation of the qubits is analyzed within a mean-field treatment. The second order phase transition is lost, while new bistable regimes occur.Comment: 5 pages, 2 figure

1,4-Dichloro­naphthalene-2,3-diol

The achiral planar (maximum deviation 0.014 Å) title compound, C10H6Cl2O2, crystallizes in the chiral space group P212121 in an arrangement incorporating conventional O—H⋯O hydrogen bonding leading to a supra­molecular chain

quality of life assessment of patients with scalp dermatitis using the italian version of the scalpdex

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Annelated medium-sized azaheterocycles as attractive scaffolds for CNS targeted leads.

Medium-sized nitrogen heterocycles (7-to-15-membered) have widespread interest in organic synthesis and medicinal chemistry. Indeed, such heterocyclic rings are found as subunits or core structures in natural and bioactive molecules, including pharmaceutical products, whereas on the other hand they often can serve as key intermediates in the synthesis of bicyclic compounds by selective transformations (e.g., transannular ring-contractions, cycloadditions). These molecular frameworks, particularly annelated 7-to-10-membered aza-heterocycles, have long drawn our attention as potential scaffolds for developing new multitarget- directed ligands (MTDLs) for treating Alzheimer's disease (AD) and other neurodegenerative syndromes.AD, the most common form of dementia affecting people worldwide, is a progressive neurodegenerative disorder, whose multifactorial pathogenesis is still not completely understood. The main histopathological changes include synaptic dysfunction and neuronal loss resulting from intracellular and extracellular fibrillar aggregates of Beta-amyloid (Abeta),hyperphosphorilated and beta-folded tau proteins, cholinergic impairment, oxidative stress, neuroinflammation, metal dys-homeostasis and mitochondrial damage. Among others, N- methyl-D-aspartate receptors (NMDARs) play a major role in learning and memory, and their overactivation causes excessive calcium influx and consequent excitotoxicity, which is associated with CNS diseases, including Parkinson's disease. Starting from our old1,2 and recent 3 findings on the suitability of partially hydrogenated benzo-, chromane-4- one- and indole-fused azepine and azocine derivatives targeted at enzymes, receptors and biochemical pathways involved in the pathogenesis of AD, we extended the investigation to novel derivatives of annelated azonines and azecines. Herein, our recent advances of benzo- and indol-fused 7-to-10-membered nitrogen heterocycles as molecular tools for AD-associated targets (e.g., butyryl- and acetylcholinesterase, monoamine oxidases A and B, Abeta aggregation, ROS insult, NMDAR antagonist), along with the results from investigation on cell and ex vivo/in vivo animal models, will be presented and discussed in an effort of rationalizing structure-activity relationships and progressing drug optimization of the examined CNS-targeted lead compounds