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101.
Novel Tacrine‐Grafted Ugi Adducts as Multipotent Anti‐Alzheimer Drugs: A Synthetic Renewal in Tacrine–Ferulic Acid Hybrids 下载免费PDF全文
Mohamed Benchekroun Dr. Manuela Bartolini Dr. Javier Egea Dr. Alejandro Romero Dr. Elena Soriano Dr. Marc Pudlo Vincent Luzet Prof. Vincenza Andrisano Dr. María‐Luisa Jimeno Dr. Manuela G. López Sarah Wehle Prof. Tijani Gharbi Prof. Bernard Refouvelet Lucía de Andrés Clara Herrera‐Arozamena Prof. Barbara Monti Prof. Maria Laura Bolognesi Prof. María Isabel Rodríguez‐Franco Prof. Dr. Michael Decker Prof. José Marco‐Contelles Dr. Lhassane Ismaili 《ChemMedChem》2015,10(3):523-539
Herein we describe the design, multicomponent synthesis, and biological, molecular modeling and ADMET studies, as well as in vitro PAMPA‐blood–brain barrier (BBB) analysis of new tacrine–ferulic acid hybrids (TFAHs). We identified (E)‐3‐(hydroxy‐3‐methoxyphenyl)‐N‐{8[(7‐methoxy‐1,2,3,4‐tetrahydroacridin‐9‐yl)amino]octyl}‐N‐[2‐(naphthalen‐2‐ylamino)2‐oxoethyl]acrylamide (TFAH 10 n ) as a particularly interesting multipotent compound that shows moderate and completely selective inhibition of human butyrylcholinesterase (IC50=68.2 nM ), strong antioxidant activity (4.29 equiv trolox in an oxygen radical absorbance capacity (ORAC) assay), and good β‐amyloid (Aβ) anti‐aggregation properties (65.6 % at 1:1 ratio); moreover, it is able to permeate central nervous system (CNS) tissues, as determined by PAMPA‐BBB assay. Notably, even when tested at very high concentrations, TFAH 10 n easily surpasses the other TFAHs in hepatotoxicity profiling (59.4 % cell viability at 1000 μM ), affording good neuroprotection against toxic insults such as Aβ1–40, Aβ1–42, H2O2, and oligomycin A/rotenone on SH‐SY5Y cells, at 1 μM . The results reported herein support the development of new multipotent TFAH derivatives as potential drugs for the treatment of Alzheimer′s disease. 相似文献
102.
Alex L. Riley Sarah E. Pepper Adam J. Canner Solomon F. Brown Mark D. Ogden 《分离科学与技术》2018,53(1):22-35
Work has been carried out screening hydrometallurgical resins for application in the valorization of industrially produced jarosite. Of the seven resins tested, anion exchange resins performed poorly for valuable metal recovery. Purolite S950+ and S957, along with a strong acid resin, show good extraction properties, but are selective for Fe3+ over the other (divalent) metals. Purolite S930+ (iminodiacetic acid-functionalized resin) demonstrates selectivity for Cu2+ over Fe3+, but poor selectivity for Ni2+, Zn2+, and Co2+. Dowex M4195 (bispicolylamine-functionalized resin) demonstrates promise for extracting metals of value away from a mixed metal pregnant liquor solution (PLS). A three-stage column-based recovery process is proposed for jarosite leachate treatment. 相似文献
103.
Discovery of a Short‐Chain Dehydrogenase from Catharanthus roseus that Produces a New Monoterpene Indole Alkaloid 下载免费PDF全文
Dr. Anna K. Stavrinides Dr. Evangelos C. Tatsis Dr. Thu‐Thuy Dang Dr. Lorenzo Caputi Dr. Clare E. M. Stevenson Dr. David M. Lawson Dr. Bernd Schneider Prof. Sarah E. O'Connor 《Chembiochem : a European journal of chemical biology》2018,19(9):940-948
Plant monoterpene indole alkaloids, a large class of natural products, derive from the biosynthetic intermediate strictosidine aglycone. Strictosidine aglycone, which can exist as a variety of isomers, can be reduced to form numerous different structures. We have discovered a short‐chain alcohol dehydrogenase (SDR) from plant producers of monoterpene indole alkaloids (Catharanthus roseus and Rauvolfia serpentina) that reduce strictosidine aglycone and produce an alkaloid that does not correspond to any previously reported compound. Here we report the structural characterization of this product, which we have named vitrosamine, as well as the crystal structure of the SDR. This discovery highlights the structural versatility of the strictosidine aglycone biosynthetic intermediate and expands the range of enzymatic reactions that SDRs can catalyse. This discovery further highlights how a sequence‐based gene mining discovery approach in plants can reveal cryptic chemistry that would not be uncovered by classical natural product chemistry approaches. 相似文献
104.
Batch leaching tests have been performed on fly ashes collected from four Australian power stations fuelled by chemically different coals. Two acidic and two alkaline fly ashes were subjected to long-term (144 h) leaching tests, and the behaviour of As, B, Mo and Se was investigated to obtain data on their potential for mobilisation during fly ash-water interactions. All four elements are mobile under different conditions and over different leaching times. The concentrations of these elements released in leaching solutions with initial pH values of 4, 7 and 10 were used to assess the influence of pH conditions on element mobility from the acidic and alkaline fly ashes. The most mobile of the four elements leached were Mo from alkaline fly ashes and B from acidic fly ashes. Arsenic concentration increased with time in leachate solutions from acidic and alkaline fly ashes; however, in solutions in contact with alkaline fly ashes the As concentration, after reaching a maximum, later decreased with time. Selenium mobility shows a similar pattern to that of As, with similar leaching concentrations. Boron has the highest relative mobility of all four elements. A process possibly responsible for the decrease in concentration of B, As and Se in alkaline leaching solutions is the formation of ettringite. Equilibrium between the solid phase (ash) and the leaching solution was not reached in any of the leaching experiments. The pH of the leaching solution is the key factor affecting the mobility of these trace elements in these fly ashes. 相似文献
105.
Surface mechanical and tribological properties of a copolymer based on benzoyl-1,4-phenylene and 1,3-phenylene were evaluated using nanoprobe investigation techniques and compared to the properties obtained at the macroscale. These copolymers are commonly referred to as self-reinforced polymers (SRPs) because of their intrinsic high strength and modulus without addition of a reinforcing agent. Specimens were prepared by spin casting, solvent casting, and compression molding. Surface mechanical properties and film thickness were measured by nanoindentation and scratching techniques. Friction properties were found using lateral force microscopy (LFM), and surface topography was imaged by tapping mode atomic force microscopy (AFM). Macroscale friction testing revealed a kinetic coefficient of friction of 0.08 for SRP, approaching that of Teflon. Similarly low relative friction coefficients were obtained in nanoprobe measurements. Nanoindentation of SRP, polycarbonate (PC), and polyetherimide (PEI) demonstrated superior surface hardness and modulus of SRP copolymer thin films. 相似文献
106.
Reviews the book, Treating the juvenile offender edited by Robert D. Hoge, Nancy G. Guerra, and Paul Boxer (see record 2008-02979-000). This book rejuvenates interest in treatment for juvenile offenders, outlining the important advances that have been made, key challenges that remain, and useful principles for effectively meeting these challenges. Key themes that are emphasised include the importance of evidence-based approaches, interventions that are sensitive to the ecological systems within which youth are embedded, and rehabilitative strategies that are closely informed by research on youths’ risks, needs, and strengths. This book does not deliver a quick manual on how to deliver a particular program, but instead carefully models how to think about and approach treatment. While the book remains accessible to beginners, it is written in a manner which will be thought-provoking and informative even for experts. Furthermore, it is likely to have the positive effect of leaving readers with a desire to learn and do more to improve current practices. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
107.
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109.
Janes Amy C.; Frederick Blaise deB.; Richardt Sarah; Burbridge Caitlin; Merlo-Pich Emilio; Renshaw Perry F.; Evins A. Eden; Fava Maurizio; Kaufman Marc J. 《Canadian Metallurgical Quarterly》2009,17(6):365
[Correction Notice: An erratum for this article was reported in Vol 18(3) of Experimental and Clinical Psychopharmacology (see record 2010-11933-011). In the article the authors find it necessary to redefine the thresholding procedure used for data analyses, due to problems in the Brain Voyager software. This does not affect the main findings of the paper.] Reactivity to smoking-related cues may play a role in the maintenance of smoking behavior and may change depending on smoking status. Whether smoking cue-related functional MRI (fMRI) reactivity differs between active smoking and extended smoking abstinence states currently is unknown. We used fMRI to measure brain reactivity in response to smoking-related versus neutral images in 13 tobacco-dependent subjects before a smoking cessation attempt and again during extended smoking abstinence (52 ± 11 days) aided by nicotine replacement therapy. Prequit smoking cue induced fMRI activity patterns paralleled those reported in prior smoking cue reactivity fMRI studies. Greater fMRI activity was detected during extended smoking abstinence than during the prequit assessment subcortically in the caudate nucleus and cortically in prefrontal (BA 6, 9, 44, 46), primary somatosensory (BA 1, 2, 3), temporal (BA 22, 41, 42), parietal (BA 7, 40) anterior cingulate (BA 24, 32), and posterior cingulate (BA 31) cortex. These data suggest that during extended smoking abstinence, fMRI reactivity to smoking versus neutral stimuli persists in brain areas involved in attention, somatosensory processing, motor planning, and conditioned cue responding. In some brain regions, fMRI smoking cue reactivity is increased during extended smoking abstinence in comparison to the prequit state, which may contribute to persisting relapse vulnerability. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
110.
Sarah J. Wakes Tanja Maegli Katharine J. Dickinson Mike J. Hilton 《Environmental Modelling & Software》2010,25(2):237-247
Numerical modelling of wind flow over complex dune topography is an ambitious prospect. There is an increasing need to understand wind flow over complex topography for land planning purposes to enable prediction of sediment transport at a particular site. New surveying techniques permit the rapid development of digital terrain models, however a stumbling block is the ability of Computational Fluid Dynamics (CFD) to emulate the wind flow over such a landscape. To overcome these difficulties, it is important to establish the parameters within which such simulations can operate. This paper details an initial two-dimensional numerical model developed in order to test various modelling assumptions against experimental field wind data. Mason Bay, Stewart Island, New Zealand was chosen as an undisturbed but accessible experimental site with a prevalent on-shore wind perpendicular to a simple foredune and a complex down-wind parabolic dune system. A complex topographical two-dimensional model with vegetation represented as a roughness was compared against field data along a transect dissecting a dune system.This paper establishes that:
- * Replicating the roughness patterns at the surface is important
- * The inlet profile should be duplicated with care
- * Modelling only a portion of the domain can have an effect on the flow patterns due to outflow effects
- * There is a modelling decision to be made between the complexity of the topography and the sophistication of the turbulence model and degree to which vegetation and sand transportation are modelled.