Search

Abstract Phosphoinositide-3-kinase-δ (PI3Kδ) is a key regulator in the process of IgE mediated mast cell degranulation, which directly induces allergic diseases, such as asthma. This study is aimed at discovery of natural PI3Kδ inhibitors from Chinese medicine and evaluating their anti-mast cell degranulation activity. A combined virtual screening based on 3D pharmacophore model and molecular docking was used to screen for bioactive ingredients directly targeting PI3Kδ. Then, an in vitro kinase inhibition assay was conducted to evaluate the PI3Kδ inhibitory activity of the virtual screening hits. Subsequently, a β-hexosaminidase release assay was performed to verify the anti-mast cell degranulation activity of the active compounds. Finally, ginkgoneolic acid was identified as a PI3Kδ inhibitor (IC 50 = 2.49 μM) and exhibited anti-mast cell degranulation activity in vitro (IC 50 = 2.40 μM). Docking studies showed that Glu826, Val827 and Val828 were key amino acid residues for PI3Kδ inhibitory activity. Ginkgoneolic acid may be a potential lead compound for developing effective and safe PI3Kδ-inhibiting drugs. Graphical abstract Image 1 Highlights • Ginkgoneolic acid derived from TCM was identified as a PI3Kδ inhibitor with IC 50 of 2.49μM. • Ginkgoneolic acid significantly inhibited degranulation of mast cellswith an IC 50 of 2.40μM. • The inhibition of ginkgoneolic acid on PI3Kδ was revealed by interacting with residues such as Glu826, Val827 and Val828. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 10A (PDE10A) has been confirmed to be an important target for the treatment of central nervous system (CNS) disorders. The purpose of the present study was to identify PDE10A inhibitors from herbs used in traditional Chinese medicine. Pharmacophore and molecular docking techniques were used to virtually screen the chemical molecule database of Sophora flavescens, a well-known Chinese herb that has been used for improving mental health and regulating the CNS. The pharmacophore model generated recognized the common functional groups of known PDE10A inhibitors. In addition, molecular docking was used to calculate the binding affinity of ligand-PDE10A interactions and to investigate the possible binding pattern. Virtual screening based on the pharmacophore model and molecular docking was performed to identify potential PDE10A inhibitors from S. flavescens. The results demonstrated that nine hits from S. flavescens were potential PDE10A inhibitors, and their biological activity was further validated using literature mining. A total of two compounds were reported to inhibit cyclic adenosine monophosphate phosphodiesterase, and one protected against glutamate-induced oxidative stress in the CNS. The remaining six compounds require further bioactivity validation. The results of the present study demonstrated that this method was a time- and cost-saving strategy for the identification of bioactive compounds from traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

A simple dispersive liquid–liquid microextraction (DLLME) method, based on retrieval of the extraction solvent by magnetic particles and followed by HPLC–UV analysis, was proposed for the determination of UV filters in environmental water samples. The new method uses vortex agitation in the DLLME process to achieve rapid equilibrium. Another feature of the proposed method is that the retrieval of the extraction solvent is accomplished by functionalized magnetic particles rather than by special designed vessels or refrigeration and thawing process associated with DLLME when low-density extraction solvent was used. The parameters that may influence the extraction, including vortex time, volume of extraction solvent, weight of the magnetic particles, volume of desorption solvent, pH, and ionic concentration of the sample solution, were investigated in detail. Under the optimized conditions, the limits of detection for the target UV filters were in range of 0.7–12.3 ng mL−1. The results also demonstrated good linearity and precision, with the regression coefficients above 0.9989 and the RSDs below 4.4%, respectively. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Good stability in aqueous solution within the pH range of 4–13. • Selective detection of Fe3+ in the presence of other cations in water. • Sensitive detection of m-dinitroaromatics. • Detection of 1,3-dinitrobenzene in aqueous phase with high sensitivity and low detection limit. A highly luminescent three-dimensional terbium-based metal organic framework [Tb(cpia)(H 2 O) 2 ] n ·nH 2 O (1) has been employed for the selective detection of m-dinitroaromatics and Fe3+. Stability tests suggest that compound 1 exhibits good stability in hot water and acidic and basic conditions within the pH range of 4–13. The strong green emission of 1 could be efficiently quenched by 1,3-dinitrobenzene, 2,4-dinitrotoluene, 2,6-dinitrotoluene in ethanol. Significantly, compound 1 can also be used to detect 1,3-dinitrobenzene in aqueous phase with high sensitivity and low detection limit (1.89 μM), indicating the detection of m-dinitroaromatics in aqueous medium can be realized. Furthermore, compound 1 also exhibits superior luminescence quenching behavior towards Fe3+ with high sensitivity and selectivity among various metal cations. In addition, the luminescence quenching mechanisms towards different analytes are also discussed in detail. These results demonstrate that compound 1 is a promising luminescent sensor for the simultaneous selective detection of m-dinitroaromatics and Fe3+ in water. [ABSTRACT FROM AUTHOR]

A novel supramolecular framework, catena-poly[[[aqua(2-phenylquinoline-4-carboxylato-κ O)silver(I)]-μ-4,4′-bipyridine-κ2 N: N′] dihydrate], {[Ag(C16H10NO2)(C10H8N2)(H2O)]·2H2O} n, has been synthesized and structurally characterized. The AgI centres are four-coordinated and bridged by 4,4′-bipyridine (4,4′-bipy) ligands to form a one-dimensional Ag-bipy chain. The Ag-bipy chains are further linked together by intermolecular O-H...O and O-H...N hydrogen-bonding interactions between adjacent chains, resulting in a three-dimensional framework. [ABSTRACT FROM AUTHOR]

In this study, a dysprosium-based metal–organic framework (MOF) sensor (Dy-MOF) was developed for the ratiometric detection of I− in aqueous medium. Upon excitation at 230 nm, Dy-MOF shows two dominant emission bands at 464 nm and 574 nm assigned to (4F, 4D)5/2 → 6H9/2 + 6F11/2 and 4F9/2 → 6H13/2 transition of Dy3+, respectively, which have different sensitivities toward iodide ions. The introduction of I− slightly weakened the blue emission at 464 nm and significantly quenched the yellow emission at 574 nm. Thus, ratiometric sensing for iodide was realized using the yellow-to-blue intensity ratio of Dy3+. Dy-MOF exhibits superior sensing behavior towards I− with high selectivity, sensitivity and low detection limit (24 nM). This study also provides a strategy for the construction of a ratiometric sensor with dual-emission bands originating from only one emission center. [ABSTRACT FROM AUTHOR]

Detection of Fe(III) and Cu(II) in water is highly desirable because their abnormal levels can cause serious harm to human health and environmental safety. In this work, a ratiometric luminescence sensing platform based on lanthanide-based silica nanoparticles was constructed for the detection of Fe3+ and Cu2+ ions. The terbium-silica nanoparticles (named SiO2@Tb) with dual-emission signals were successfully prepared by grafting Tb3+ ions onto trimellitic anhydride (TMA) functionalized silica nanospheres. It can serve as a ratiometric fluorescent probe for the detection of Fe3+ and Cu2+ ions in water with the green emission of Tb3+ ions as a response signal and the blue emission of silica nanospheres as the reference signal. Significantly, an easy-to-differentiate color change for visual detection was also realized. SiO2@Tb shows high sensitivity even in very low concentration regions towards the sensing of Fe3+ and Cu2+ with low detection limits of 0.75 μM and 0.91 μM, respectively. Moreover, the mechanism for the luminescence quenching of SiO2@Tb was systematically investigated, and was attributed to the synergetic effect of the absorption competition quenching (ACQ) mechanism and cation exchange. This study demonstrates that SiO2@Tb can be employed as a promising fluorescent probe for the detection of Fe3+ and Cu2+ ions, and the combination of lanthanide ions with silica nanoparticles is an effective strategy to construct a ratiometric fluorescent sensing platform for the determination of analytes in environmental detection. [ABSTRACT FROM AUTHOR]

A luminescence sensor based on an europium(III)-based lanthanide–organic framework, [Eu(BCB)(DMF)]·(DMF)1.5(H2O)2 (1), was synthesized via a solvothermal method using 4,4′,4′′-benzenetricarbonyltribenzoic acid (H3BCB) as a bridging ligand. Single-crystal X-ray diffraction indicates that Eu centers are eight-coordinated with a trigonal dodecahedron and a square antiprismatic configuration, and adjacent Eu atoms are bridged by BCB organic linkers to form a 3D rod-packing structure. Photoluminescence studies show that compound 1 emits bright red luminescence and behaves as a multi-responsive luminescent sensor toward 4-nitrophenol (4-NP) and I− and Fe3+ ions in water with high sensitivity, selectivity and low detection limits. Furthermore, the possible luminescence sensing mechanisms were also investigated by PXRD analysis, UV-vis spectroscopy and X-ray photoelectron spectroscopy (XPS). The recognition mechanism for 4-NP and I− ions can be attributed to the competition absorption and that for Fe3+ ions is considered to be a multi-quenching mechanism dominated by competition absorption. This study demonstrates that the lanthanide-based MOF might be a promising candidate for the detection of 4-NP and I− and Fe3+ ions in aqueous medium. [ABSTRACT FROM AUTHOR]

A potent luminescent sensor for the detection of iodide ions was developed based on a terbium(III)-based lanthanide–organic framework [Tb(cpia)(H2O)2]n·nH2O (1), which was prepared under hydrothermal conditions using the 5-(4-carboxyphenoxy)isophthalic acid (H3cpia) bridging ligand. Compound 1 exhibits superior luminescence quenching behavior towards I− with high sensitivity and selectivity among various anions and shows real-time response. Moreover, the mechanism of the selective luminescence quenching response for I− can be mainly explained by the absorption competition between 1 and I−. According to this quenching mechanism, we find that compound 1 can also detect Br− by adjusting the excitation wavelength. Significantly, this work could serve as a general guidance for the design and synthesis of pollutant sensors. [ABSTRACT FROM AUTHOR]

Poly(9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one) (PPTC) was synthesized by the microwave-assisted ring-opening polymerization (MROP) of a six-membered cyclic carbonate monomer 9-phenyl-2,4,8,10-tetraoxaspiro-[5,5]undcane-3-one (PTC) with tin(II) 2-ethylhexanoate (Sn(Oct)) or aluminum isopropoxide (Al(OPr)) as the catalysts. The obtained polycarbonates were further reduced by apalladium/carbonate catalyst (10% Pd/C) to afford partly deprotected polycarbonates containing hydroxyl groups (HPPTC). These two types of polycarbonates were characterized by H-NMR, Fourier transform infrared spectroscopy (FTIR), UV, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and automatic contact-angle measurements. The influence of the feed molar ratio of monomer-to-catalyst, the microwave irradiation power and the reaction time on the polymerization was also studied. The experimental results showed that HPPTC possessed significantly higher hydrophilicity and water absorption rate than PPTC. [ABSTRACT FROM AUTHOR]

A water-soluble fullerenol containing porphyrin and isoindoline nitroxide groups APTSPP-C60(OH)10-(TMIO)3was synthesized by the incorporation of 5-(4-amino-phenyl)-10,15,20-tris(4-sulfonatophenyl)-porphyrin (APTSPP) as a tumor-targeting group and 5-formyl-1,1,3,3-tetramethylisoindolin-2-yloxyl (FTMIO) into fullerenol C60(OH)11. This nonmaterial was further characterized by FT-IR, UV, MS, TEM, fluorescence, etc. and its properties in vitro were also evaluated. Electrochemical experiments indicated that APTSPP-C60(OH)10-(TMIO)3retained similar electrochemical properties and redox reaction mechanisms as 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO). Electron paramagnetic resonance (EPR) spectra of APTSPP-C60(OH)10-(TMIO)3exhibited the hyperfine splittings and characteristic spectra of CTMIO, with typical nitroxide g-values and nitrogen isotropic hyperfine coupling constants. In vitro cytotoxicity assay showed APTSPP-C60(OH)10-(TMIO)3possessed low cytotoxicities to human renal tubular epithelial 293T cells and HepG-2 cells. Therefore APTSPP-C60(OH)10-(TMIO)3may be considered as a potential candidate for novel biological spin probe using EPR spectroscopy. [ABSTRACT FROM AUTHOR]

Diethylenetriaminepentaacetic di(L-dopa ethyl ester) ligand (DTPA-2LDEE) was synthesized by reaction between diethylenetriaminepentaacetic dianhydride (DTPAA) and L-dopa ethyl ester (LDEE). This ligand reacted with gadolinium chloride and sodium pertechnetate to make the corresponding neutral gadolinium complex Gd-DTPA-2LDEE and technetium-99m-labeled complex99mTc-DTPA-2LDEE, respectively. The ligand and complexes were characterized and their propertiesin vitroandin vivowere also evaluated. Gd-DTPA-2LDEE possessed higher relaxation effectiveness and lower cytotoxicity to human hepatoma HepG-2 cells than Gd-DTPA.99mTc-DTPA-2LDEE had enhanced single-photon emission computed tomography (SPECT) signal enhancements of the kidneys in rats and provided longer duration time than that of99mTc-DTPA. Therefore,99mTc-DTPA-2LDEE can be selectively excreted by the kidneys and used as a potential radioactive probe in SPECT. [ABSTRACT FROM AUTHOR]

Compounds with strong intramolecular hydrogen bonds (e.g., salicylic acid) have weak intermolecular hydrogen bonding interactions between them and functional monomers in the imprinting process. Consequently, the corresponding molecularly imprinted polymers (MIPs) have no specific adsorption ability. Here, the first magnetic dummy MIPs (MDMIPs) based on benzonic acid as dummy template are successfully developed and evaluated with respect to the applications in selective enrichment and analysis of salicylic acid from complex mixtures. Various parameters affecting absorption/desorption were evaluated for achieving optimal recovery and reducing nonspecific interactions. The prepared MDMIPs showed high adsorption capacity, good selectivity, rapid kinetic binding (40 min) and magnetic separation (5 s), high reproducibility (RSD< 4 % for batch-to-batch evaluation), and stability (only 4 % decrease after 6 cycles). Owing to the efficacy in specific binding and removal of interference, trace level salicylic acid was quantified (0.2 μg/g of fresh mass) in Actinidia chinensis by high-performance liquid chromatography. [ABSTRACT FROM AUTHOR]

Abstract: Porphyrin-containing polyaspartamide ligands (APTSPP–PHEA–DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4′-aminophenyl)-10,15,20-tris(4′-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP–PHEA–DTPA–Gd). Experimental data of 1H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP–PHEA–DTPA–Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd–DTPA. Moreover, APTSPP–PHEA–DTPA–Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. [Copyright &y& Elsevier]