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241.
Chern JH Chang CS Tai CL Lee YC Lee CC Kang IJ Lee CY Shih SR 《Bioorganic & medicinal chemistry letters》2005,15(19):4206-4211
The new pyridyl imidazolidinone derivative, 1-[5-(4'-chlorobiphenyl-4-yloxy)-3-methylpentyl]-3-pyridin-4-yl-imidazolidin-2-one (+/-)-1a, was synthesized and found to have an excellent antiviral activity against EV71 (IC50 = 0.009 microM). Therefore, both the enantiomers, (S)-(+)-1a and (R)-(-)-1a, have been prepared starting from readily available monomethyl (R)-3-methylglutarate (7) as a useful chiral building block and their antiviral activity was evaluated in a plaque reduction assay. Interestingly, we observed that the enantiomer (S)-(+)-1a was 10-fold more active against enterovirus71 (EV71) (IC50 = 0.003 microM) than the corresponding enantiomer (R)-(-)-1a (IC50 = 0.033 microM). Similar results were found against all five strains (1743, 2086, 2231, 4643, and BrCr) of EV71 tested. This demonstrated that the absolute configuration of the chiral carbon atom at the 3-position of the alkyl linker considerably influenced the anti-EV71 activity of these pyridyl imidazolidinones. 相似文献
242.
Fink BE Vite GD Mastalerz H Kadow JF Kim SH Leavitt KJ Du K Crews D Mitt T Wong TW Hunt JT Vyas DM Tokarski JS 《Bioorganic & medicinal chemistry letters》2005,15(21):4774-4779
A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities. 相似文献
243.
Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors
Chen LR Wang YC Lin YW Chou SY Chen SF Liu LT Wu YT Kuo CJ Chen TS Juang SH 《Bioorganic & medicinal chemistry letters》2005,15(12):3058-3062
N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC50 values ranging from 0.95 to 17.50 microM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin. 相似文献
244.
Beneficial effect of silkworm hemolymph on a CHO cell system: Inhibition of apoptosis and increase of EPO production 总被引:5,自引:0,他引:5
To produce erythropoietin (EPO), Chinese hamster ovary (CHO) cells were first cultured in a medium containing FBS (growth medium) and then in a serum-free medium containing sodium butyrate (production medium). Sodium butyrate increases recombinant protein production, but also induces apoptosis, which reduces cell viability and productivity. In a previous study, we found that silkworm hemolymph (SH), an insect serum, inhibits the apoptosis of insect and mammalian cells. To overcome sodium butyrate-induced apoptosis, we added SH to growth medium. This pretreatment with SH inhibited the sodium butyrate-induced apoptosis of CHO cells and consequently increased their longevity and their ability to produce EPO. As a result, the volumetric productivity of EPO was increased five-fold. SH was found to inhibit cytochrome c release from mitochondria into the cytosol, and prevented the activation of caspase-3 and other subsequent caspase reactions. 相似文献
245.
246.
The population structure of domesticated species is influenced by the natural history of the populations of predomesticated ancestors, as well as by the breeding system and complexity of the breeding practices exercised by humans. Within Oryza sativa, there is an ancient and well-established divergence between the two major subspecies, indica and japonica, but finer levels of genetic structure are suggested by the breeding history. In this study, a sample of 234 accessions of rice was genotyped at 169 nuclear SSRs and two chloroplast loci. The data were analyzed to resolve the genetic structure and to interpret the evolutionary relationships between groups. Five distinct groups were detected, corresponding to indica, aus, aromatic, temperate japonica, and tropical japonica rices. Nuclear and chloroplast data support a closer evolutionary relationship between the indica and the aus and among the tropical japonica, temperate japonica, and aromatic groups. Group differences can be explained through contrasting demographic histories. With the availability of rice genome sequence, coupled with a large collection of publicly available genetic resources, it is of interest to develop a population-based framework for the molecular analysis of diversity in O. sativa. 相似文献
247.
248.
Sawcer S Ban M Maranian M Yeo TW Compston A Kirby A Daly MJ De Jager PL Walsh E Lander ES Rioux JD Hafler DA Ivinson A Rimmler J Gregory SG Schmidt S Pericak-Vance MA Akesson E Hillert J Datta P Oturai A Ryder LP Harbo HF Spurkland A Myhr KM Laaksonen M Booth D Heard R Stewart G Lincoln R Barcellos LF Hauser SL Oksenberg JR Kenealy SJ Haines JL;International Multiple Sclerosis Genetics Consortium 《American journal of human genetics》2005,77(3):454-467
To provide a definitive linkage map for multiple sclerosis, we have genotyped the Illumina BeadArray linkage mapping panel (version 4) in a data set of 730 multiplex families of Northern European descent. After the application of stringent quality thresholds, data from 4,506 markers in 2,692 individuals were included in the analysis. Multipoint nonparametric linkage analysis revealed highly significant linkage in the major histocompatibility complex (MHC) on chromosome 6p21 (maximum LOD score [MLS] 11.66) and suggestive linkage on chromosomes 17q23 (MLS 2.45) and 5q33 (MLS 2.18). This set of markers achieved a mean information extraction of 79.3% across the genome, with a Mendelian inconsistency rate of only 0.002%. Stratification based on carriage of the multiple sclerosis–associated DRB1*1501 allele failed to identify any other region of linkage with genomewide significance. However, ordered-subset analysis suggested that there may be an additional locus on chromosome 19p13 that acts independent of the main MHC locus. These data illustrate the substantial increase in power that can be achieved with use of the latest tools emerging from the Human Genome Project and indicate that future attempts to systematically identify susceptibility genes for multiple sclerosis will have to involve large sample sizes and an association-based methodology. 相似文献
249.
Ajuebor MN Aspinall AI Zhou F Le T Yang Y Urbanski SJ Sidobre S Kronenberg M Hogaboam CM Swain MG 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(12):8027-8037
Fulminant liver failure (FLF) consists of a cascade of events beginning with a presumed uncontrolled systemic activation of the immune system. The etiology of FLF remains undefined. In this study, we demonstrate that CCR5 deficiency promotes the development of acute FLF in mice following Con A administration by preventing activated hepatic CD1d-restricted NKT cells (but not conventional T cells) from dying from activation-induced apoptosis. The resistance of CCR5-deficient NKT cells from activation-induced apoptosis following Con A administration is not due to a defective Fas-driven death pathway. Moreover, FLF in CCR5-deficient mice also correlated with hepatic CCR5-deficient NKT cells, producing more IL-4, but not IFN-gamma, relative to wild-type NKT cells. Furthermore, FLF in these mice was abolished by IL-4 mAb or NK1.1 mAb treatment. We propose that CCR5 deficiency may predispose individuals to the development of FLF by preventing hepatic NKT cell apoptosis and by regulating NKT cell function, establishing a novel role for CCR5 in the development of this catastrophic liver disease that is independent of leukocyte recruitment. 相似文献
250.
Cephalosporin C production by immobilized Cephalosporium acremonium cells in a repeated batch tower bioreactor 总被引:1,自引:0,他引:1
The industrial production of antibiotics with filamentous fungi is usually carried out in conventional aerated and agitated tank fermentors. Highly viscous non-Newtonian broths are produced and a compromise must be found between convenient shear stress and adequate oxygen transfer. In this work, cephalosporin C production by bioparticles of immobilized cells of Cephalosporium acremonium ATCC 48272 was studied in a repeated batch tower bioreactor as an alternative to the conventional process. Also, gas-liquid oxygen transfer volumetric coefficients, k(L)a, were determined at various air flow-rates and alumina contents in the bioparticle. The bioparticles were composed of calcium alginate (2.0% w/w), alumina ( < 44 micra), cells, and water. A model describing the cell growth, cephalosporin C production, oxygen, glucose, and sucrose consumption was proposed. To describe the radial variation of oxygen concentration within the pellet, the reaction-diffusion model forecasting a dead core bioparticle was adopted. The k(L)a measurements with gel beads prepared with 0.0, 1.0, 1.5, and 2.0% alumina showed that a higher k(L)a value is attained with 1.5 and 2.0%. An expression relating this coefficient to particle density, liquid density, and air velocity was obtained and further utilized in the simulation of the proposed model. Batch, followed by repeated batch experiments, were accomplished by draining the spent medium, washing with saline solution, and pouring fresh medium into the bioreactor. Results showed that glucose is consumed very quickly, within 24 h, followed by sucrose consumption and cephalosporin C production. Higher productivities were attained during the second batch, as cell concentration was already high, resulting in rapid glucose consumption and an early derepression of cephalosporin C synthesizing enzymes. The model incorporated this improvement predicting higher cephalosporin C productivity. 相似文献