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61.
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
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Katherine L. Frank Sarah E. Exley Travis L. Thornell Sarah E. Morgan Jeffrey S. Wiggins 《Polymer》2012,53(21):4643-4651
Dispersion of monoamine-functionalized polyhedral oligomeric silsesquioxane (POSS) in an epoxy network was improved by pre-reacting the POSS with excess epoxide and employing a high-temperature cure. DGEBA/DDS networks were formulated with 2.5 and 10 wt% POSS. In some samples, POSS was pre-reacted with DGEBA. The hybrid materials were characterized via SEM, TEM, and DMA. The microscopy and DMA results evinced a multiscale morphology with POSS-rich glassy domains, nano- and microcrystallites, and crystallite agglomerations. For a loading level of 2.5 wt% POSS, the sample with unmodified POSS cured at 125 °C had inorganic crystallites on the order of 1–5 μm and agglomerations on the order of 10–20 μm, whereas the sample with pre-reacted POSS cured at 180 °C had near-perfect dispersion with no agglomerations and very few POSS crystallites. The 10 wt% POSS epoxies also showed improved dispersion with pre-reaction and increasing cure temperature. The dispersion improvements were attributed to the enhanced miscibility of the pre-reacted POSS and the increased rate of POSS reaction into the growing epoxy network at a higher cure temperature. 相似文献
64.
Sarah Pourjafar Ahmad Rahimpour Mohsen Jahanshahi 《Journal of Industrial and Engineering Chemistry》2012,18(4):1398-1405
Novel polyethersulfone (PES)/poly (vinyl alcohol) (PVA)/titanium dioxide (TiO2) composite nanofiltration membranes were prepared by dip-coating of PES membrane in PVA and TiO2 nanoparticles aqueous solution. Glutaraldehyde (GA) was used as a cross-linker for the composite polymer membrane in order to enhance the chemical, thermal as well as mechanical stabilities. TiO2 nanoparticles with different concentrations (0, 0.05, 0.1, 0.5 wt.%) were coated on the surface of PVA/PES composite membrane. The morphological study was investigated by atomic force microscopy (AFM), scanning surface microscopy (SEM) and along with X-ray diffraction (XRD). In addition, the membranes performances, in terms of permeate flux, ion rejection and swelling factor were also investigated. It was found that the increase in TiO2 solution concentration can highly affect the surface morphology and filtration performance of coated membranes. The contact angle measurement and XRD studies indicated that the TiO2 nanoparticles successfully were coated on the surface of PVA/PES composite membranes. However, rougher surface was obtained for membranes by TiO2 coating. The filtration performance data showed that the 0.1 wt.% TiO2-modified membrane presents higher performance in terms of flux and NaCl salt rejection. Finally, TiO2 modified membranes demonstrated the lower degree of swelling. 相似文献
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66.
Ahmadreza Rashedi Mohammad Sarabian Mohammadhossein Firouznia Dallas Roberts Guillaume Ovarlez Sarah Hormozi 《American Institute of Chemical Engineers》2020,66(12):e17100
We present an experimental study on the shear-induced migration and axial development of particles in the channel flows of non-Brownian suspensions. The suspending fluid is Newtonian. We investigate fracturing flows with a Hele-Shaw type scaling through building a unique channel setup and an advanced optical system. The local particle concentration profiles are measured via the refractive-index matching technique for a wide range of bulk volume fraction, that is, . Simultaneously, the particle image velocimetry is performed to determine the velocity profile of the particle phase. We compare our experimental results with the available two-phase continuum frameworks and show discrepancies and similarities in the fully developed and axial development of the solid volume fraction profiles. We discuss directions in which the continuum frameworks require improvements. 相似文献
67.
Dr. Sandra Junghänel Sarah Karczewski Sandra Bäcker Prof. Dr. Shirley K. Knauer Prof. Dr. Carsten Schmuck 《Chembiochem : a European journal of chemical biology》2017,18(22):2268-2279
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure–activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection. 相似文献
68.
Sarah Gilgunn Keefe Murphy Henning Stckmann Paul J. Conroy T. Brendan Murphy R. William Watson Richard J. OKennedy Pauline M. Rudd Radka Saldova 《International journal of molecular sciences》2020,21(23)
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies. 相似文献
69.
Insa Thale Sarah Maskri Lucie Grey Luca Matteo Todesca Prof. Dr. Thomas Budde Dr. Ivan Maisuls Prof. Dr. Cristian A. Strassert Prof. Dr. Oliver Koch Prof. Dr. Albrecht Schwab Prof. Dr. Bernhard Wünsch 《ChemMedChem》2023,18(2):e202200551
The Ca2+ activated K+ channel KCa3.1 is overexpressed in several human tumor cell lines, e. g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this KCa3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [18F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of KCa3.1 channels in lung adenocarcinoma cells in mice. The novel senicapoc BODIPY conjugates with two F-atoms ( 9 a ) and with a F-atom and a methoxy moiety ( 9 b ) at the B-atom led to the characteristic punctate staining pattern resulting from labeling of single KCa3.1 channels in A549-3R cells. This punctate pattern was completely removed by preincubation with an excess of senicapoc confirming the high specificity of KCa3.1 labeling. Due to the methoxy moiety at the B-atom and the additional oxyethylene unit in the spacer, 9 b exhibits higher polarity, which improves solubility and handling without reduction of fluorescence quantum yield. Docking studies using a cryo-electron microscopy (EM) structure of the KCa3.1 channel confirmed the interaction of 9 a and 9 b with a binding pocket in the channel pore. 相似文献
70.
Geert R. Verheyen Filip Meersman Isabelle Noyens Sarah Goossens Sabine Van Miert 《European Journal of Lipid Science and Technology》2023,125(3):2200193
The depletion of natural resources, the increasing use of valuable land surface for human activities, and the generation of waste are detrimental to the planet. Sustainable alternatives to guarantee a sufficient supply of food, feed, and biomaterials are needed. Insects may hold an interesting position in a circular economy to tackle contemporary societal challenges. Using insects for food, feed, biomaterial production, and to valorize side-streams, have gained increased interest. Mealworms are amenable to large-scale farming. Herein, the potential of mealworm oil for implementation in a cosmetic hand cream is evaluated. It is shown that mealworms are rich in oil (≈30% of the dry weight), and the oil can be extracted using hexane or ethyl acetate as a solvent. The euthanization step of mealworms has profound effect on the free fatty acid content. The fatty acid profile indicates a large proportion of unsaturated fatty acids, which is promising for use in cosmetic applications. In a proof of concept, the mealworm oil is implemented in a hand cream and compared to hand cream containing macadamia nut oil. No differences in odor and aspect/stability are observed, but mealworm creams are slightly less white color. Mealworm oil is suitable for cosmetics applications. Practical applications: Several insect species can be sustainably reared on low-value organic side-streams, requiring only small amounts of land-surface, less water, and producing less greenhouse gases. In addition, they have short life cycles and can be reared continuously and locally. This implies that insects are an interesting source of biological materials including proteins and oils. Insect oils, including oil of mealworms, have interesting fatty acid profiles that make them amenable to replace oils of vegetable origin for applications within cosmetics. The results indicate that mealworm oil can be a novel, sustainable ingredient for use in the cosmetics industry. 相似文献