Synthesis,In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1–16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including ¹H, ¹³CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure–activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.     

Simultaneous Quantification of Opioids in Blood and Urine by Gas Chromatography-Mass Spectrometer with Modified Dispersive Solid-Phase Extraction Technique

Common methodologies such as liquid-liquid extraction and solid-phase extraction are applied for the extraction of opioids from biological specimens i.e., blood and urine. Techniques including LC-MS/LC-MSMS, GC-MS, etc. are used for qualitative or quantitative determination of opioids. The goal of the present work is to design a green, economic, rugged, and simple extraction technique for famous opioids in human blood and urine and their simultaneous quantification by GC-MS equipped with an inert plus electron impact (EI) ionization source at SIM mode to produce reproducible and efficient results. Morphine, codeine, 6-acetylmorphine, nalbuphine, tramadol and dextromethorphan were selected as target opioids. Anhydrous Epsom salt was applied for dSPE of opioids from blood and urine into acetonitrile extraction solvent with the addition of sodium phosphate buffer (pH 6) and n-hexane was added to remove non-polar interfering species from samples. BSTFA was used as a derivatizing agent for GC-MS. Following method validation, the LOD/LLOQ and ULOQ were determined for morphine, codeine, nal-buphine, tramadol, and dextromethorphan at 10 ng/mL and 1500 ng/mL, respectively, while the LOD/LLOQ and ULOQ were determined for 6-acetylmorphine at 5 ng/mL and 150 ng/mL, respectively. This method was applied to real blood and urine samples of opioid abusers and the results were found to be reproducible with true quantification.     

Classification of low energy sign-changing solutions of an almost critical problem

In this paper we make the analysis of the blow up of low energy sign-changing solutions of a semilinear elliptic problem involving nearly critical exponent. Our results allow to classify these solutions according to the concentration speeds of the positive and negative part and, in high dimensions, lead to complete classification of them. Additional qualitative results, such as symmetry or location of the concentration points are obtained when the domain is a ball.     

Visible-Light-Promoted Switchable Selective Oxidations of Styrene Over Covalent Triazine Frameworks in Water

Using photocatalytic oxidation to convert basic chemicals into high value compounds in environmentally benign reaction media is a current focus in catalytic research. The challenge lies in gaining controllability over product formation selectivity. We design covalent triazine frameworks as heterogeneous, metal-free, and recyclable photocatalysts for visible-light-driven switchable selective oxidation of styrene in pure water. Selectivity in product formation was achieved by activation or deactivation of the specific photogenerated oxygen species. Using the same photocatalyst, by deactivation of photogenerated H₂O₂, benzaldehyde was obtained with over 99 % conversion and over 99 % selectivity as a single product. The highly challenging and sensitive epoxidation of styrene was carried out by creating peroxymonocarbonate as an initial epoxidation agent in the presence of bicarbonate, which led to formation of styrene oxide with a selectivity up to 76 % with near quantitative conversion. This study demonstrates a preliminary yet interesting example for simple control over switchable product formation selectivity for challenging oxidation reactions of organic compounds in pure water.     

Two Novel Compounds Built Up of Decavanadate Clusters and Transition-Metal Complexes: Synthesis and Structure

Two inorganic compounds entitled tetrasodium hexaaquacobalt decavanadate tetraco-sahydrate,(I), and diammonium bis[hexaaquamanganese] decavanadate tetrahydrate,(II), have been isolated by conventional solution method and structurally characterized by single-crystal X-ray diffraction methods, scanning electron microscopy, IR spectra, thermal analyses and cyclic voltammetry measurements. They crystallize with triclinic (P-1) symmetry and consists of a centrosymmetric [V₁₀O₂₈]^6? anion. The Co²⁺ and Mn²⁺ cations in (I) and (II) respectively are octahedrally coordinated by six water molecules. Compound (I) also contains a polymeric linear array of edge-sharing [Na(OH₂)₆]⁺ and [Co(OH2)₆]²⁺ octahedra and compound (II) exhibit a catenary structure consisting of [V₁₀O₂₈]^6? anions linked to [Mn(OH2)₆]²⁺ and NH₄ ⁺via hydrogen bonds.     

Synthesis of alkynes and alkynyl iodides bearing a protected amino alcohol moiety as functionalized amino acids precursors

Amino acid precursors in protected amino alcohol form are important synthons that can be used as building-blocks for the hemisynthesis of non-natural amino acids. Serine can be used as a common starting material for the synthesis of such compounds differently protected. Particularly, protected amino alcohols bearing an ethynyl and/or an iodoethynyl group can be used in cross-couplings, in 1,3-dipolar cycloadditions and/or in Nozaki-Hiyama-Kishi type reactions. We thus demonstrated that the efficiently protected amino alcohols derived from serine can be coupled to a sugar derivative by an indium mediated alkynylation reaction. The conditions of this coupling are compatible with such functionalized derivatives and allow envisaging an access to C-glycosylated amino acids.     

Bahri-Coron type theorem for the scalar curvature problem on high dimensional spheres

We consider the existence and multiplicity results for the prescribed scalar curvature problem on the standard spheres of high dimension n ?? 7. Given a C ² positive function K, using the theory of critical points at infinity, we prove an existence result as Bahri-Coron theorem. Our case is a generalization of Li (J Differ Equ 120:319?C410, 1995). Indeed, here the function K is flat near some critical points as in Li (J Differ Equ 120:319?C410, 1995) and it can have some nondegenerate critical points with ?? K ?? 0. Furthermore, using some topological arguments, we prove another kind of result.     

Construction of solutions of an elliptic PDE with a supercritical exponent nonlinearity using the finite dimensional reduction

In this paper, we construct some solutions of an elliptic PDE with a supercritical exponent nonlinearity. We follow the ideas of Bahri–Li–Rey (Calc Var Partial Differ Equ V.3:67–93, 1995) by using the finite dimensional reduction.     

Carbon-13 NMR of some organophosphorus compounds. 2—chemical shifts and P?C coupling constants of diaryl-, dialkoxy- and diaryloxy-phosphine amines with general formula Y2PNRR'

Carbon-13 chemical shifts and ²J(POC), ³J(POCC), ²J(PNC) and ³J(PNC) coupling constants of 30 compounds containing the amine moiety, with the general formula Y₂PNRR' (Y ? C₆H₅, CH₃O, CH₃CH₂O, CH₂O; Y₂ ? 1,2-dioxybenzene) have been determined. J(PNC) values have been used to explain the preferred conformation around the P? N bond. A comparison between ²J(PNC) and ²J(PNH) was accomplished.