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31.
Back Cover: Insight into the Interactions between Novel Coumarin Derivatives and Human A3 Adenosine Receptors (ChemMedChem 10/2014) 下载免费PDF全文
32.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds 下载免费PDF全文
Dr. Sandeep Sundriyal Dr. Nicholas A. Malmquist Dr. Joachim Caron Scott Blundell Dr. Feng Liu Xin Chen Nitipol Srimongkolpithak Prof. Jian Jin Prof. Susan A. Charman Prof. Artur Scherf Dr. Matthew J. Fuchter 《ChemMedChem》2014,9(10):2360-2373
Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1 ), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads. 相似文献
33.
Insight into the Functional and Structural Properties of 3‐Arylcoumarin as an Interesting Scaffold in Monoamine Oxidase B Inhibition 下载免费PDF全文
34.
A wave of recent cross-national research has pointed to the positive consequences for countries with high levels of “quality of government” (QoG), broadly defined, such as corruption, impartiality, and quality of public services. Yet the question of how QoG varies at the sub-national level is still widely overlooked, in particular with measures that are available over time. To address it, we present the third round of data from the regional European Quality of Government Index (EQI) survey corruption (D73), Europe (N44) governance (H11); sub-national (R50), time series (C22), collected in 2017 and built upon the opinions of 78,000 respondents in 193 regions from 21 European countries. The data provides several contributions to the literature. First, while the majority of QoG-type indices rely on expert assessments, the EQI relies on the assessments of citizens, who are the on-the-ground consumers of public services. Second, the data begins to show trends on QoG variation over time, as well as across European regions. Consequently, this data is the most comprehensive sub-national data to date; mapping of QoG within and across EU countries over the past decade. Building on previous rounds of data collected in 2010 and 2013, the 2017 EQI, which is published free for scholarly use, builds on both perceptions and experiences of citizens in public service areas such as health care, education, and law enforcement. This paper presents the results of the latest survey, improved with respect to the previous ones, discussion of trends across space and over time, as well as interesting avenues for future research that we detect across European regions. 相似文献
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36.
Elisabeth Lichtenberger A. Subbakrishniah Milton H. Grannatt rd Antoine S. Bailly Charles G. Schmidt Dougald A. MacFarlane Rudolf Andorka Ernesto Quintanilla L. B. Wallerstein Stan Openshaw Herman G. Berkman Kingsley E. Haynes W. W. Hall Jr. Richard B. Le Heron John E. Stapleford Alan Pearman Paul Soyke Thomas R. Beard Howard F. Newell Michael Dear Kenneth D. Lawrence Peter Mastenbroek Rolf B. Schmitt Sung Woong Hong A. A. Horner James M. Murray Donald W. Jones W. E. Mullendore 《The Annals of Regional Science》1977,11(3):129-183
37.
Nitrogen gas distributions in sediment pore water were determined for cores collected in Lake Erie and two nearby harbors. Concentrations of N2 gas ranged from 11.9 to 37.0 ml l−1 and from 8.9 to 58.3 ml l−1 for open lake and polluted harbor sediments, respectively. Maximum concentrations in the harbor sediments were as high as 3.5 times N2 saturation calculated for the overlying water. Indirect diffusive flux estimates for nitrogen gas ranged from 20 to 32% of the particulate nitrogen sedimentation rate in Lake Erie. At one location, the amount of nitrogen gas lost by diffusion was calculated to be greater than the nitrogen deposited to the sediments. Nitrogen gas production and diffusive loss from surficial sediments probably represents a major pathway for nitrogen removal from Lake Erie. 相似文献
38.
Estuarine sediments are often highly enriched in particle-reactive metal contaminants and because aquatic animals have often been shown to acquire metals predominantly from their diet, benthic animals feeding on deposited or resuspended sediments may also accumulate metals through this uptake pathway. Laboratory experiments were performed in which the surface deposit-feeding polychaete, Nereis succinea, was exposed to As(+ 5), Cd, and Cr(+ 3) in pore water or in estuarine sediments with and without enrichment with algal debris. These experiments generated metal uptake parameters (assimilation efficiency of ingested metal [AE], uptake rate constant of dissolved metal, efflux rate constants following dietary or aqueous metal exposures) used in a kinetic model of metal bioaccumulation. The model showed that > 97% of the body burden of these metals is accumulated through ingested sediment. The kinetic model was further modified to consider the geochemical fractionation of the metals in the sediments because metals bound to some fractions were shown to be unavailable to these polychaetes. The modified model substituted the AE term for each metal by the percentage of metal extracted in neutral and weak acid exchangeable fractions (termed “carbonex” fraction) multiplied by the slope of the regression between the metal AE and its fractionation in carbonex. The modified model generated predictions of As, Cd, and Cr body burdens in polychaetes at three different estuarine sites that matched independent field observations at these sites (r2 = 0.84 for sediments without organic enrichment, r2 = 0.87 with organic enrichment). Model predictions that relied on total metal concentrations showed weaker relationships (r2 = 0.11-0.50). This study adds to the evidence for the dominance of dietary uptake of metals in aquatic animals and identifies a key sedimentary fraction of metals that can account for bioavailability of sediment-bound metals. 相似文献
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40.
Dr. Rachel S. Heath Jack J. Sangster Prof. Nicholas J. Turner 《Chembiochem : a European journal of chemical biology》2022,23(7):e202200075
The enantioselective oxidation of 2° alcohols to ketones is an important reaction in synthetic chemistry, especially if it can be achieved using O2-driven alcohol oxidases under mild reaction conditions. However to date, oxidation of secondary alcohols using alcohol oxidases has focused on activated benzylic or allylic substrates, with unactivated secondary alcohols showing poor activity. Here we show that cholesterol oxidase (EC 1.1.3.6) could be engineered for activity towards a range of aliphatic, cyclic, acyclic, allylic and benzylic secondary alcohols. Additionally, since the variants demonstrated high (S)-selectivity, deracemisation reactions were performed in the presence of ammonia borane to obtain enantiopure (R)-alcohols. 相似文献