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991.
992.
Alzheimer’s disease (AD) is a debilitating neurodegenerative disease that affects over 47 million people worldwide, and is the most common form of dementia. There is a vast body of literature demonstrating that the disease is caused by an accumulation of toxic extracellular amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles that consist of hyperphosphorylated tau. Adherence to the Mediterranean diet has been shown to reduce the incidence of AD and the phenolic compounds in extra virgin olive oil, including oleocanthal, have gained a significant amount of attention. A large number of these ligands have been described in the pre-existing literature and 222 of these compounds have been characterised in the OliveNet™ database. In this study, molecular docking was used to screen the 222 phenolic compounds from the OliveNet™ database and assess their ability to bind to various forms of the Aβ and tau proteins. The phenolic ligands were found to be binding strongly to the hairpin-turn of the Aβ1−40 and Aβ1−42 monomers, and binding sites were also identified in the tau fibril protein structures. Luteolin-4′-O-rutinoside, oleuricine A, isorhoifolin, luteolin-7-O-rutinoside, cyanidin-3-O-rutinoside and luteolin-7,4-O-diglucoside were predicted to be novel lead compounds. Molecular dynamics (MD) simulations performed using well-known olive ligands bound to Aβ1−42 oligomers highlighted that future work may examine potential anti-aggregating properties of novel compounds in the OliveNet™ database. This may lead to the development and evaluation of new compounds that may have efficacy against Alzheimer’s disease. 相似文献
993.
Ruiguang Xu Jiahua Weng Liwen Hu Guangneng Peng Zhihua Ren Junliang Deng 《Natural product research》2018,32(18):2244-2247
The purpose of this study was to investigate the anti-Newcastle disease virus (NDV) activities of 9-oxo-10,11-dehydroageraphorone (euptox A) from Eupatorium adenophorum Spreng (E. adenophorum) in vitro. NDV infection of chicken embryo fibroblasts (CEFs) was performed. Cytotoxicities and antiviral activities of euptox A was assessed by the MTT method. The interaction of NDV with cell membrane protein was detected by virus overlay protein binding assay (VOPBA). The expression levels of NDV genes in CEFs was tested by RTFQ PCR. The results showed that the maximal safe concentrations of euptox A to CEFs was 10 μg/mL. Euptox A could directly neutralise NDV, inhibit the infectivity of NDV to CEFs and block intracellular NDV treat NDV infection. And euptox A brings competitiveness inhibition for NDV binding to its receptors and then prevent NDV infection. These results indicated that euptox A possessed anti-NDV activity has potential use as components of a natural antiviral drug. 相似文献
994.
995.
Dongqin Yu Yijia Guan Fuquan Bai Zhi Du Nan Gao Prof. Jinsong Ren Prof. Xiaogang Qu 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(14):3489-3495
Recently, photooxygenation of amyloid β (Aβ) has emerged as an effective way to inhibit Aβ aggregation in Alzheimer's disease (AD) treatment. However, their further application has been highly obstructed by self-aggregation, no metal chelating ability, and poor protein-enrichment capacity. Herein, porphyrinic metal–organic frameworks (PMOFs) are utilized as a superior CuII chelating and photooxidation agent for inhibiting Aβ aggregation. We selected only four classical kinds of POMFs (Zr–MOF, Al–MOF, Ni–MOF, Hf–MOF) for further investigation in our study, which are stable in physiological conditions and exhibit excellent biocompatibility. Among them, Hf–MOF was the most efficient Aβ photooxidant. A possible explanation about the difference in capacity of 1O2 generation of these four PMOFs has been provided according to the experimental results and DFT calculations. Furthermore, Hf–MOFs are modified with Aβ-targeting peptide, LPFFD. This can not only enhance Hf–MOFs targeting cellular Aβ to decrease Aβ-induced cytotoxicity, but also improve Aβ photooxidation in the complicated living environment. More intriguingly, in vivo studies indicate that the well-designed LPFFD modified Hf–MOFs can decrease Aβ-induced neurotoxicity and extend the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Our work may open a new avenue for using MOFs as neurotoxic-metal-chelating and photo-therapeutic agents for AD treatment. 相似文献
996.
997.
Aggregation of amyloid β-peptide (Aβ) into insoluble fibrils is a key pathological event in Alzheimer’s disease (AD). Under
certain conditions, Cu(II) exhibits strong inhibitory effect on the Zn(II)-induced aggregation, which occurs significantly
even at nearly physiological concentrations of zinc ion in vitro. Cu(II) is considered as a potential factor in the normal brain preventing Aβ from aggregating. The possible mechanism of
the inhibitory effect of Cu(II) is investigated for the first time by molecular modeling method. In the mono-ring mode, the
Y10 residue promotes typical quasi-helix conformations of Aβ. Specially, [Cu-H13(NTT)-Y10(OH)] complex forms a local 3.010 helix conformation. In the multi-ring mode, the side chains of Q15 and E11 residues collaborate harmoniously with other chelating
ligands producing markedly low energies and quasi-helix conformations. [Cu-3N-Q15(O)-E11(O1)] and [Cu-H13(NTT)-Y10(OH)] complex
with quasi-helix conformations may prefer soluble forms in solution. In addition, hydrogen-bond interactions may be the main
driving force for Aβ aggregation. All the results will provide helpful clues for an improved understanding of the role of
Cu(II) in the pathogenesis of AD and contribute to the development of an “anti-amyloid” therapeutic strategy. 相似文献
998.
Perceptual ratings of hoarseness and breathiness were used to assess the efficacy of two intensive methods for treating dysarthrophonia in individuals with idiopathic Parkinson disease. One method emphasized phonatory-respiratory effort (the Lee Silverman Voice Treatment, LSVT®) and the other emphasized respiratory effort alone (RET). Perceptual ratings were performed by two expert listeners based on random order presentation of the patients' pretreatment and posttreatment recordings of the “Rainbow Passage.” The listeners were blinded to the patients and their treatment group. Statistically significant pretreatment to posttreatment improvement in hoarseness and breathiness was observed in the LSVT® group but not in the RET group. The present findings are consistent with acoustic and physiologic findings reported previously, providing further evidence for the efficacy of the LSVT®. 相似文献
999.
Modified TLC bioautographic method for screening acetylcholinesterase inhibitors from plant extracts
Zhongduo Yang Xu Zhang Dongzhu Duan Zhuwen Song Mingjun Yang Shuo Li 《Journal of separation science》2009,32(18):3257-3259
The present work describes modifications to an existing TLC bioautographic method for detecting acetylcholinesterase inhibitors from plant extracts. The basic principle of the method is that the enzyme converts 1‐naphthyl acetate into naphthol which reacts with Fast Blue B salt to make a purple‐colored background on the TLC plates. Inhibitors of acetylcholinesterases produced white spots on the background. Our modifications involve changes in the concentration of the enzyme, the reagents, and the time of the reaction. With these changes, the consumption of the enzyme was reduced by 85% and the detection limits were decreased remarkably. 相似文献
1000.
Gerhard Bringmann Robert-Michael Pfeifer Kristina Hartner Reto Brun Eva-Maria Peters 《Tetrahedron》2004,60(30):6335-6344
A broad variety of enantiopure axially chiral 2-aminomethyl-1-(2-oxyphenyl)naphthalenes were prepared via short and efficient synthetic pathways by using the ‘lactone method’ for the regio- and stereoselective construction of the biaryl axis. Their in vitro activity against Trypanosoma cruzi, the causative agent of Chagas' disease, was evaluated. In particular, the M-configured atropisomers, with the 2-oxy function equipped with an O-triflate group, were found to exhibit good antitrypanosomal activities (down to IC50=1.6 μg/mL), combined with low levels of cytotoxicity. 相似文献