Effect of Hydrolyzable Tannins on Glucose-Transporter Expression and Their Bioavailability in Pig Small-Intestinal 3D Cell Model

Intestinal transepithelial transport of glucose is mediated by glucose transporters, and affects postprandial blood-glucose levels. This study investigates the effect of wood extracts rich in hydrolyzable tannins (HTs) that originated from sweet chestnut (Castanea sativa Mill.) and oak (Quercus petraea) on the expression of glucose transporter genes and the uptake of glucose and HT constituents in a 3D porcine-small-intestine epithelial-cell model. The viability of epithelial cells CLAB and PSI exposed to different HTs was determined using alamarBlue^®. qPCR was used to analyze the gene expression of SGLT1, GLUT2, GLUT4, and POLR2A. Glucose uptake was confirmed by assay, and LC–MS/ MS was used for the analysis of HT bioavailability. HTs at 37 µg/mL were found to adversely affect cell viability and downregulate POLR2A expression. HT from wood extract Tanex at concentrations of 4 µg/mL upregulated the expression of GLUT2, as well as glucose uptake at 1 µg/mL. The time-dependent passage of gallic acid through enterocytes was influenced by all wood extracts compared to gallic acid itself as a control. These results suggest that HTs could modulate glucose uptake and gallic acid passage in the 3D cell model.     

4-Phenethyl-1-Propargylpiperidine-Derived Dual Inhibitors of Butyrylcholinesterase and Monoamine Oxidase B

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer’s disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13–15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC₅₀ of 4.3 µM) and hBChE (IC₅₀ of 8.5 µM). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs     

Finite Rank Perturbations of Toeplitz Operators

We study finite rank perturbations of the Brown-Halmos type results involving products of Toeplitz operators acting on the Bergman space.      

A New Generation of Anticancer Drugs: Mesoporous Materials Modified with Titanocene Complexes

The next generation : The grafting of titanocene complexes on the surfaces of MCM‐41 and SBA‐15 led to a new generation of anticancer drugs, which are very active against human cancer cells.

     

Photochemical transformation of β,β′-dithienyl substituted o-divinylbenzenes leading to 1,2-dihydronaphthalenes or fused pentacyclic compounds: first evidence of electrocyclization process via 2,3-dihydronaphthalene intermediates

The photochemical behaviour of 2,2′-(o-phenylenedivinylene)dithiophenes (7a–c), 3,3′-(o-phenylenedivinylene)dithiophene (8a) and 3,3′-(o-phenylenedivinylene)dibenzothiophene (8b) was studied under the low concentrations. An intramolecular reaction via the 2,3-dihydronaphthalene intermediate has been observed in all studied examples accompanied by dimerization and polymerization. The 1,2-dihydro-2,3-dithienylnaphthalenes (9a–c) were isolated (7–9%) from the 2-thiophene derivatives while the 3-thiophene derivatives gave polycyclic structures (13–44% yield).     

Nonpeptidic Selective Inhibitors of the Chymotrypsin‐Like (β5 i) Subunit of the Immunoproteasome

Elevated expression of the immunoproteasome has been associated with autoimmune diseases, inflammatory diseases, and various types of cancer. Selective inhibitors of the immunoproteasome are not only scarce, but also almost entirely restricted to peptide‐based compounds. Herein, we describe nonpeptidic reversible inhibitors that selectively block the chymotrypsin‐like (β5i) subunit of the human immunoproteasome in the low micromolar range. The most potent of the reversibly acting compounds were then converted into covalent, irreversible, nonpeptidic inhibitors that retained selectivity for the β5i subunit. In addition, these inhibitors discriminate between the immunoproteasome and the constitutive proteasome in cell‐based assays. Along with their lack of cytotoxicity, these data point to these nonpeptidic compounds being suitable for further investigation as β5i‐selective probes for possible application in noncancer diseases related to the immunoproteasome.     

Kinetics and mechanism of the substitution reactions of some bifunctional palladium(II) complexes with different nitrogen-donor heterocycles

Substitution reactions of three Pd(II) complexes, [Pd(cbdca)Cl₂]^2? (cbdca = cyclobutane-1,1-dicarboxylato), [Pd(ox)Cl₂]^2? (ox = oxalato) and [Pd(mal)Cl₂]^2? (mal = malonato), with different five- and six-membered N-heterocycles, such as pyrazole, 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazine, imidazole, pyridazine and pyrimidine, were investigated in aqueous 0.10 M NaClO₄ with the presence of 20 mM NaCl using variable-temperature stopped-flow spectrophotometry. Substitution of these complexes occurs in two consecutive reversible steps, and their reactivity decreases in order [Pd(cbdca)Cl₂]^2? > [Pd(mal)Cl₂]^2? > [Pd(ox)Cl₂]^2?. The most reactive nucleophile among the five-membered heterocycles is imidazole, while pyridazine is the most reactive among the six-membered heterocycles. Activation parameters were determined for all reactions, and negative values for entropy of activation, ΔS^≠, support an associative mode of substitution. The reaction between [Pd(mal)Cl₂]^2? complex and pzBr was investigated by ¹H NMR, and the obtained results confirm that substitution with nitrogen-donor nucleophile does not lead to decomposition of the complex.