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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.
Discovery of Quinoline‐Derived Trifluoromethyl Alcohols,Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model 下载免费PDF全文
Prof. Dr. Vinoth Sittaramane Jihan Padgett Philip Salter Ashley Williams Shauntelle Luke Rebecca McCall Prof. Dr. Jonathan F. Arambula Vincent B. Graves Mark Blocker David Van Leuven Keturah Bowe Julia Heimberger Hannah C. Cade Supriya Immaneni Prof. Dr. Abid Shaikh 《ChemMedChem》2015,10(11):1802-1807
In this study the rational design, synthesis, and anticancer activity of quinoline‐derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp3‐C?H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4‐trifluoro‐3‐hydroxy‐3‐(quinolin‐2‐ylmethyl)butanoate ( 1 ), 2‐benzyl‐1,1,1‐trifluoro‐3‐(quinolin‐2‐yl)propan‐2‐ol ( 2 ), and trifluoro‐3‐(isoquinolin‐1‐yl)‐2‐(thiophen‐2‐yl)propan‐2‐ol ( 3 ). Compounds 2 and 3 were found to be more toxic than compound 1 ; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2 , with an LC50 value of 14.14 μm , has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents. 相似文献
103.
Vincent A. Hackley Ungyu Paik Bong-Ho Kim Subhas G. Malghan 《Journal of the American Ceramic Society》1997,80(7):1781-1788
An aqueous-based system (Si-Al2 O3 -Y2 O3 -Fe2 O3 ) for processing sintered reaction-bonded silicon nitride (SRBSN) was investigated with an emphasis on chemical control of suspension component interactions. Chemical stability and dispersion properties of a commercial silicon powder were characterized using electroacoustic, adsorption isotherm, and rheological measurements. The interactions of silicon with nitriding agent, sintering aids, dispersants, and binder were considered. The effects of pH, electrolyte, aging, particle size, and solids loading were examined. The suspension properties of the silicon powder were influenced by the native oxide film and powder treatment history. The silicon-oxide composite particles exhibit dispersion behavior similar to silica, characterized by a negative surface potential above pH 2. A method to improve the dispersion and homogeneity of suspension components based on the use of quaternary amine dispersants is proposed. 相似文献
104.
Dai-Hua Tsai Nadia Amyai Pedro Marques-Vidal Jia-Lin Wang Michael Riediker Vincent Mooser Fred Paccaud Gerard Waeber Peter Vollenweider Murielle Bochud 《Particle and fibre toxicology》2012,9(1):1-9
Background
Particulate air pollution is associated with increased risk of cardiovascular disease and stroke. Although the precise mechanisms underlying this association are still unclear, the induction of systemic inflammation following particle inhalation represents a plausible mechanistic pathway.Methods
We used baseline data from the CoLaus Study including 6183 adult participants residing in Lausanne, Switzerland. We analyzed the association of short-term exposure to PM10 (on the day of examination visit) with continuous circulating serum levels of high-sensitive C-reactive protein (hs-CRP), interleukin 1-beta (IL-1??), interleukin 6 (IL-6), and tumor-necrosis-factor alpha (TNF-??) by robust linear regressions, controlling for potential confounding factors and assessing effect modification.Results
In adjusted analyses, for every 10???g/m3 elevation in PM10, IL-1? increased by 0.034 (95?% confidence interval, 0.007-0.060) pg/mL, IL-6 by 0.036 (0.015-0.057) pg/mL, and TNF-?? by 0.024 (0.013-0.035) pg/mL, whereas no significant association was found with hs-CRP levels.Conclusions
Short-term exposure to PM10 was positively associated with higher levels of circulating IL-1?, IL-6 and TNF-?? in the adult general population. This positive association suggests a link between air pollution and cardiovascular risk, although further studies are needed to clarify the mechanistic pathway linking PM10 to cardiovascular risk. 相似文献105.
Ellen Chan Siu N. Leung Muhammad O. Khan Hani E. Naguib Francis Dawson Vincent Adinkrah 《大分子材料与工程》2012,297(10):1014-1020
Multifunctional materials that are lightweight and thermally conductive but electrically insulating are important for modern electronics, computer, and telecommunication technologies. Here, a novel foam structure of a polymer/matrix composite filled with ceramic platelets with improved thermal conductivity is reported. Such improvement is caused by the stress‐induced alignment of thermally conductive fillers in the cell wall of the plastic foam. The foam structure is very promising for use as a lightweight electronic packaging material owing to its light weight, thermal conduction ability, electrical insulation, and good processability.
106.
Adam Same Vincent Battaglia Hong-Yue Tang Jae Wan Park 《Journal of Applied Electrochemistry》2012,42(1):1-9
Overcharge of lithium-ion batteries can lead to the deposition of lithium ions on the surface of graphite electrodes. The
phenomenon of lithium deposition causes reduced electrochemical performance and presents safety concerns for lithium-ion batteries
in high-power applications. This study presents a technique using neutron radiography (NR) for in situ visualization of the
effects of overcharge in a graphite/NCA (LiNi0.8Co0.15Al0.05O2) lithium-ion cell. Patterns of deposition of solid material on the surface of the graphite electrode observed in the radiographs
were confirmed by direct observation of the electrode. Inductively coupled plasma mass spectrometry was used to verify the
elemental contents of the deposited material. NR is shown to be a promising tool for the study of lithium-ion batteries in
high-power applications. 相似文献
107.
Lucile Lallemant Gilbert Fantozzi Vincent Garnier Guillaume Bonnefont 《Journal of the European Ceramic Society》2012,32(11):2909-2915
Starting from a commercial slurry of high purity α-Al2O3, freeze-dried powders, cast, filter-pressed or cold isostatically pressed samples were produced. Resulting powders or green bodies showing different particles packing were densified by spark plasma sintering (SPS) to obtain transparent polycrystalline α-Al2O3. Microstructure and real in-line transmittance (RIT) after SPS were dependent on the particles packing quality. Avoiding large agglomerates, narrowing the pore size distribution, reducing the most-frequent pore size (Dmode) and avoiding macroscopic heterogeneities within the green bodies enabled high RIT values to be achieved in the visible and near-infrared spectrum. However, a limit was achieved in the preparation of green bodies for which reducing the Dmode had no more influence on the optical behaviour of samples sintered by SPS. Finally, pure α-Al2O3 samples presenting a high RIT640 nm value of 53% were produced from all the green bodies obtained by the following techniques: filter-pressing, slip casting and cold isostatic pressing. 相似文献
108.
Matthieu Picher Hugo Navas Raul Arenal Etienne Quesnel Eric Anglaret Vincent Jourdain 《Carbon》2012,50(7):2407-2416
The influence of the temperature and precursor pressure on the defect density of single-walled carbon nanotubes (SWCNTs) grown by catalytic chemical vapor deposition was studied for several catalyst–precursor couples. The SWCNT defect density was assessed by studying the Raman D band. In situ Raman monitoring was used to determine experimental conditions allowing the preparation of samples free of pyrolytic carbon and not altered by air exposure. The most striking feature is that the Arrhenius plots of the IG/ID ratio systematically display a convex shape, i.e. the apparent activation energy decreases with increasing temperature. From HRTEM observations and oxidation experiments, this evolution of the D band features is ascribed to the catalytic growth of long SWCNTs with few defects at high temperature and of short and defective SWCNTs and carbon structures at low temperature. The convex Arrhenius behavior is well accounted by two kinetic models: (i) a model considering a change of intermediate states as a function of the temperature (for instance due to a phase transition of the catalyst particle or a change of intermediate carbon species) and (ii) a model considering a high-temperature process of defect creation (for instance by reaction with reactive gas species). 相似文献
109.
Dr. Lina Liang Tong-You Wade Wei Pei-Yu Wu Wouter Herrebout Ming-Daw Tsai Prof. Stéphane P. Vincent 《Chembiochem : a European journal of chemical biology》2020,21(20):2982-2990
d -Glycero-d -manno-heptose-1β,7-bisphosphate (HBP) and d -glycero-d -manno-heptose-1β-phosphate (H1P) are bacterial metabolites that were recently shown to stimulate inflammatory responses in host cells through the activation of the TIFA-dependent NF-κB pathway. To better understand structure-based activity in relation to this process, a family of nonhydrolyzable phosphonate analogues of HBP and H1P was synthesized. The inflammation modulation by which these molecules induce the TIFA-NF-κB signal axis was evaluated in vivo at a low-nanomolar concentration (6 nM) and compared to that of the natural metabolites. Our data showed that three phosphonate analogues had similar stimulatory activity to HBP, whereas two phosphonates antagonized HBP-induced TIFA-NF-κB signaling. These results open new horizons for the design of pro-inflammatory and innate immune modulators that could be used as vaccine adjuvant. 相似文献
110.
Benjamin D. Fallen Katy Rainey Carl E. Sams Dean A. Kopsell Vincent R. Pantalone 《Journal of the American Oil Chemists' Society》2012,89(7):1333-1343
Increasing oleic acid, a monounsaturated fatty acid, is reported to strike the best balance between cold flow properties and oxidative stability in soybean seed oil to enhance biodiesel and produce a better burning fuel. In addition, it is important that elevated oleic acid soybeans have the agronomic traits of local cultivars and maintain oleic acid stability across environments. Research was conducted in 2007–2008 to evaluate six Roundup Ready® soybean recombinant inbred lines exhibiting enhanced levels of oleic acid. The six elevated oleic lines averaged a 55% increase in oleic acid and a 43% decrease in linolenic acid over the two commercial cultivars (AG3906 and AG4103). Some elevated oleic acid genotypes fulfilled the linear regression definition of a stable genotype. TN03-93RR was the best genotype because of its oleic acid content (397 g kg?1) and desirable regression estimates for stability. Iodine value (IV), peroxide value (PV), and induction period (IP) were used to evaluate the fuel properties of the two lines with the highest oleic acid content and the two commercial cultivars. The elevated oleic acid lines had significantly better IP, PV and IV for better biodiesel properties and oxidative stability than the two commercial cultivars. 相似文献