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排序方式: 共有1056条查询结果,搜索用时 12 毫秒
71.
Xiang-Yang Ye Stephanie Chen Hao Zhang Kenneth T. Locke Kevin O’Malley Litao Zhang Raijit Srivastava Bowman Miao Daniel Meyers Hossain Monshizadegan Debra Search Denise Grimm Rongan Zhang Jonathan Lippy Celeste Twamley Jodi K. Muckelbauer Chiehying Chang Yongmi An Vinayak Hosagrahara Lisa Zhang Joseph A. Tino 《Bioorganic & medicinal chemistry letters》2010,20(9):2933-2937
The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPARα/γ dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPARα versus PPARγ. Potent, highly selective PPARα activators 2a and 2l, as well as PPARα activators with significant PPARγ activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed. 相似文献
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Arabidopsis thaliana grown in soil amended with barley grain inocula of Penicillium simplicissimum GP17-2 or receiving root treatment with its culture filtrate (CF) exhibited clear resistance to Pseudomonas syringae pv. tomato DC3000 (Pst). To assess the contribution of different defense pathways, Arabidopsis genotypes implicated in salicylic acid (SA) signaling expressing the NahG transgene or carrying disruption in NPR1 (npr1), jasmonic acid (JA) signaling (jar1) and ethylene (ET) signaling (ein2) were tested. All genotypes screened were protected by GP17-2 or its CF. However, the level of protection was significantly lower in NahG and npr1 plants than it was in similarly treated wild-type plants, indicating that the SA signaling pathway makes a minor contribution to the GP17-2-mediated resistance and is insufficient for a full response. Examination of local and systemic gene expression revealed that GP17-2 and its CF modulate the expression of genes involved in both the SA and JA/ET signaling pathways. Subsequent challenge of GP17-2-colonized plants with Pst was accompanied by direct activation of SA-inducible PR-2 and PR-5 genes as well as potentiated expression of the JA-inducible Vsp gene. In contrast, CF-treated plants infected with Pst exhibited elevated expression of most defense-related genes (PR-1, PR-2, PR-5, PDF1.2 and Hel) studied. Moreover, an initial elevation of SA responses was followed by late induction of JA responses during Pst infection of induced systemic resistance (ISR)-expressing plants. In conclusion, we hypothesize the involvement of multiple defense mechanisms leading to an ISR of Arabidopsis by GP17-2. 相似文献
75.
Hossain MT Soga K Wakabayashi K Kamisaka S Fujii S Yamamoto R Hoson T 《Journal of plant physiology》2007,164(4):385-393
Effects of silicon on the mechanical and chemical properties of cell walls in the second leaf of oat (Avena sativa L.) seedlings were investigated. The cell wall extensibility in the basal region of the second leaf was considerably higher than that in the middle and subapical regions. Externally applied silicon increased the cell wall extensibility in the basal region, but it did not affect the extensibility in the middle and subapical regions. The amounts of cell wall polysaccharides and phenolic compounds, such as diferulic acid (DFA) and ferulic acid (FA), per unit length were lower in the basal region than in the middle and subapical regions of the leaf, and silicon altered these amounts in the basal region. In this region, silicon decreased the amounts of matrix polymers and cellulose per unit length and of DFA and FA, both per unit length and unit matrix polymer content. Silicon treatment also lowered the activity of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) in the basal region. In contrast, the amount of silicon in cell walls increased in response to silicon treatment in three regions. These results suggest that in the basal region, silicon reduces the net wall mass and the formation of phenolic acid-mediated cross-linkages between wall polysaccharides. Such modifications of wall architecture may be responsible for the silicon-induced increase in the cell wall extensibility in oat leaves. 相似文献
76.
Zawacka-Pankau J Issaeva N Hossain S Pramanik A Selivanova G Podhajska AJ 《The Journal of biological chemistry》2007,282(4):2466-2472
Photodynamic therapy (PDT) of cancer is an alternative treatment for tumors resistant to chemo- and radiotherapy. It induces cancer cell death mainly through generation of reactive oxygen species by a laser light-activated photosensitizer. It has been suggested that the p53 tumor suppressor protein sensitizes some human cancer cells to PDT. However, there is still no direct evidence for this. We have demonstrated here for the first time that the photosensitizer protoporphyrin IX (PpIX) binds to p53 and disrupts the interaction between p53 tumor suppressor protein and its negative regulator HDM2 in vitro and in cells. Moreover, HCT116 colon cancer cells exhibited a p53-dependent sensitivity to PpIX in a dose-dependent manner, as was demonstrated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and fluorescence-activated cell sorter (FACS) analysis of cell cycle profiles. We have also observed induction of p53 target pro-apoptotic genes, e.g. puma (p53-up-regulated modulator of apoptosis), and bak in PpIX-treated cells. In addition, p53-independent growth suppression by PpIX was detected in p53-negative cells. PDT treatment (2 J/cm2) of HCT116 cells induced p53-dependent activation of pro-apoptotic gene expression followed by growth suppression and induction of apoptosis. 相似文献
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Sclerotinia sclerotiorum is a fungal pathogen, which causes stem rot in crucifer crops and in several other plant families resulting in enormous yield losses all over the world. Brassinin is a phytoalexin produced by crucifer plants as part of a general defense mechanism against pathogens and other forms of stress. To the great detriment of crucifers, some fungal pathogens, as for example S. sclerotiorum, can detoxify brassinin. Detoxification of brassinin via glucosylation of the indole nitrogen is carried out by an inducible glucosyltransferase produced in S. sclerotiorum. Because brassinin is a precursor of several phytoalexins active against S. sclerotiorum, brassinin glucosyltransferase (BGT) is a potentially useful metabolic target to control S. sclerotiorum. Toward this end, we have designed, synthesized, and screened several brassinin analogues using both mycelial cultures and cell-free homogenates of S. sclerotiorum. A noticeable decrease in the rate of brassinin detoxification in cell cultures was observed in the presence of methyl (benzofuran-3-yl)methyldithiocarbamate, methyl (benzofuran-2-yl)methyldithiocarbamate, methyl (indol-2-yl)methyldithiocarbamate, 3-phenylindole, 6-fluoro-3-phenylindole, and 5-fluorocamalexin. In addition, these compounds caused substantial inhibition of BGT activity (ca. 80%) in cell-free homogenates of S. sclerotiorum, while only brassinin and 3-phenylindole were transformed to the corresponding beta-d-1-glucopyranosyl products. These results indicate that, although many other glucosyltransferases appear to be produced by S. sclerotiorum in cell cultures, BGT is substrate specific. Overall these results show that selective and potent inhibitors of BGT can be developed. 相似文献
79.
A series of 5-arylidene-2,4-thiazolidinediones and its geranyloxy or prenyloxy derivative were synthesized and studied for their radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Their comparable scavenging activities were expressed as IC50 value. Compounds 2c, 2d, 4d, and 6a showed appreciable radical scavenging activities. The vanillin based thiazolidinedione compound 2c displayed highest activity comparable to that of alpha-tocopherol. But in vivo, compound 6a showed better results in inducing phase II detoxifying/antioxidative enzyme. 相似文献
80.
Tomato (Solanum lycopersicum L.) is called ‘the poor man’s orange’ due to its low price and improved nutritional values. An experiment was conducted to study the breeding potential of some exotic tomato lines by assessing various qualitative and quantitative traits conferring yield and quality attributes. Among the qualitative traits, greater variability was observed for growth type, stem hairiness, and fruit shape and size. A determinate growth habit was observed in the genotype AVTO9802 while the genotype AVTO0102 produced yellow color fruits. A significant (p ≤ 0.01) variation was also observed for the studied quantitative traits. Based on yield and traits attributed to yield, the genotypes AVTO0314, GPB0107, GPB0120 and AVTO9802 were selected as promising genotypes. The differences between the genotypic and phenotypic coefficients of variation (GCV and PCV) of the studied quantitative traits were very low. This suggests that the apparent variation was mainly due to the genotypes. The higher GCV and PCV values were observed for the number of primary branches plant−1 (NPB), number of fruits cluster−1 (NFC), individual fruit weight (IFW) and total soluble solids (TSS). High heritability was recorded for all quantitative traits in a broad sense. However, the individual fruit diameter showed the highest heritability (99.56). The highest (102.75) genetic advance (GA) was observed for the number of fruits plant−1 (NFP). High heritability coupled with high GA as percentage of mean were recorded for the traits NFP, NFC, fruit yield plant−1 (FYP) and IFW. FYP showed a significant positive correlation with NFC (0.714***) and a negative correlation with days to the first harvest (−0.539***) and plant height (−0.492**). Principal component analysis revealed that the first four components explained 78.5% of the total variation among the genotypes. Thus, the promising genotypes (AVTO0314, GPB0107, GPB0120, AVTO9802 and AVTO0102) isolated from this study can be used for developing high-yielding and high-quality tomato varieties. 相似文献