Combinations of Piperine with Hydroxypropyl-β-Cyclodextrin as a Multifunctional System

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase).     

Magnetic Resonance Signal Amplification by Reversible Exchange of Selective PyFALGEA Oligopeptide Ligands Towards Epidermal Growth Factor Receptors

The biorelevant PyFALGEA oligopeptide ligand, which is selective towards the epidermal growth factor receptor (EGFR), has been successfully employed as a substrate in magnetic resonance signal amplification by reversible exchange (SABRE) experiments. It is demonstrated that PyFALGEA and the iridium catalyst IMes form a PyFALGEA:IMes molecular complex. The interaction between PyFALGEA:IMes and H₂ results in a ternary SABRE complex. Selective 1D EXSY experiments reveal that this complex is labile, which is an essential condition for successful hyperpolarization by SABRE. Polarization transfer from parahydrogen to PyFALGEA is observed leading to significant enhancement of the ¹H NMR signals of PyFALGEA. Different iridium catalysts and peptides are inspected to discuss the influence of their molecular structures on the efficiency of hyperpolarization. It is observed that PyFALGEA oligopeptide hyperpolarization is more efficient when an iridium catalyst with a sterically less demanding NHC ligand system such as IMesBn is employed. Experiments with shorter analogues of PyFALGEA, that is, PyLGEA and PyEA, show that the bulky phenylalanine from the PyFALGEA oligopeptide causes steric hindrance in the SABRE complex, which hampers hyperpolarization with IMes. Finally, a single-scan ¹H NMR SABRE experiment of PyFALGEA with IMesBn revealed a unique pattern of NMR lines in the hydride region, which can be treated as a fingerprint of this important oligopeptide.     

New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.     

爱立信IMS weShare分享每一天(系列之二)如何提供出色的用户体验?

爱立信IMS weShare业务有20%的开发与用户视觉体验相关(用户界面、图标、标签以及进度条),其它的80%则主要致力于设备间的系统.与此相对比,用户的体验则完全(100%)有赖于其可接触的事物.     

Acidity and basicity of hydrotalcite derived mixed Mg-Al oxides studied by test reaction of MBOH conversion and temperature programmed desorption of NH3 and CO2

Mg-Al hydrotalcites intercalated with five different interlayer anions—CO₃²⁻, SO₄²⁻, Cl⁻, HPO₄²⁻ or terephthalate—were synthesized by either the coprecipitation or ion-exchange method. The structure of the as-synthesized samples and the presence of intended anions in the interlayer gallery of hydrotalcites were determined by X-ray diffraction and FTIR spectroscopy. On calcination at 600 °C the materials were transformed into mixed metal oxides. The kind of the counterbalancing anions present in the parent hydrotalcite influences strongly textural parameters of the obtained Mg-Al oxides. Both temperature-programmed desorption of NH₃ and CO₂, and test reaction of 2-methyl-3-butyn-2-ol (MBOH) conversion were used to determine the acidity and basicity of the samples. The hydrotalcite derived mixed Mg-Al oxides showed the presence of Brønsted and Lewis acid and base sites. However, the strong basic character of the solids caused that acetone and acetylene were observed as the major products of MBOH conversion.     

Efficient computer implementation of the renormalized coupled-cluster methods: The R-CCSD[T], R-CCSD(T), CR-CCSD[T], and CR-CCSD(T) approaches

The recently proposed renormalized (R) and completely renormalized (CR) coupled-cluster (CC) methods of the CCSD[T] and CCSD(T) types have been implemented using recursively generated intermediates and fast matrix multiplication routines. The details of this implementation, including the complete set of equations that have been used in writing efficient computer codes, memory requirements, and typical CPU timings, are discussed. The R-CCSD[T], R-CCSD(T), CR-CCSD[T], and CR-CCSD(T) computer codes and similar codes for the standard CC methods, including the LCCD, CCD, CCSD, CCSD[T], and CCSD(T) approaches, have been incorporated into the gamess package. Information about the main features of this new set of CC programs is provided.     

On the modelling of thermo-unelastic periodic composites: Microlocal parameter theory

Summary In this paper a new high efficiency C-O grid coupled with the potential flow solver based on the finite volume technique is given. It significantly reduces the CPU time and increases the computational efficiency. In order to improve the accuracy of traditional potential method a shock point operator is used to account for entropy correction. Some calculated results of 2D inviscid, viscous/inviscid interaction and 3D inviscid flow indicate that nonisentropic potential method produces results closer to Euler solution as well as experimental data, while its computational efforts are nearly the same as the usual isentropic potential method.With 9 Figures