排序方式: 共有146条查询结果,搜索用时 15 毫秒
41.
Appendino G Ech-Chahad A Minassi A Bacchiega S De Petrocellis L Di Marzo V 《Bioorganic & medicinal chemistry letters》2007,17(1):132-135
Starting from ROPA (2), analogues of RTX (1a) modified on the acyl side chain were prepared and evaluated for vanilloid activity in HEK-293 cells over-expressing the human recombinant TRPV1. The ROPA motif provided an enhancement of potency sufficient to expand the range of vanillyl surrogates to structural elements (e.g., an unsubstituted phenyl ring) that afford inactive analogues in compounds from the capsaicin series. 相似文献
42.
Hannah Nguyen Abdellah Allali-Hassani Stephen Antonysamy Shawn Chang Lisa Hong Chen Carmen Curtis Spencer Emtage Li Fan Tarun Gheyi Fengling Li Shichong Liu Joseph R. Martin David Mendel Jonathan B. Olsen Laura Pelletier Tatiana Shatseva Song Wu Feiyu Fred Zhang Cheryl H. Arrowsmith Peter J. Brown Robert M. Campbell Benjamin A. Garcia Dalia Barsyte-Lovejoy Mary Mader Masoud Vedadi 《The Journal of biological chemistry》2015,290(22):13641-13653
SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. However, the mechanism(s) by which SMYD2 promotes oncogenesis is not understood. A small molecule probe for SMYD2 would allow for the pharmacological dissection of this biology. In this report, we disclose LLY-507, a cell-active, potent small molecule inhibitor of SMYD2. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. A 1.63-Å resolution crystal structure of SMYD2 in complex with LLY-507 shows the inhibitor binding in the substrate peptide binding pocket. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys370 at submicromolar concentrations. We used LLY-507 to further test other potential roles of SMYD2. Mass spectrometry-based proteomics showed that cellular global histone methylation levels were not significantly affected by SMYD2 inhibition with LLY-507, and subcellular fractionation studies indicate that SMYD2 is primarily cytoplasmic, suggesting that SMYD2 targets a very small subset of histones at specific chromatin loci and/or non-histone substrates. Breast and liver cancers were identified through in silico data mining as tumor types that display amplification and/or overexpression of SMYD2. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. These findings suggest that LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes. 相似文献
43.
Laurent Hébert Pauline Bidaud Didier Goux Abdellah Benachour Claire Laugier Sandrine Petry 《Current microbiology》2014,68(3):352-357
Lysozyme is an important and widespread component of the innate immune response that constitutes the first line of defense against bacterial pathogens. The bactericidal effect of this enzyme relies on its capacity to hydrolyze the bacterial cell wall and also on a nonenzymatic mechanism involving its cationic antimicrobial peptide (CAMP) properties, which leads to membrane permeabilization. In this paper, we report our findings on the lysozyme resistance ability of Rhodococcus equi, a pulmonary pathogen of young foals and, more recently, of immunocompromised patients, whose pathogenic capacity is conferred by a large virulence plasmid. Our results show that (i) R. equi can be considered to be moderately resistant to lysozyme, (ii) the activity of lysozyme largely depends on its muramidase action rather than on its CAMP activity, and (iii) the virulence plasmid confers part of its lysozyme resistance capacity to R. equi. This study is the first one to demonstrate the influence of the virulence plasmid on the stress resistance capacity of R. equi and improves our understanding of the mechanisms enabling R. equi to resist the host defenses. 相似文献
44.
Benjahad A Guillemont J Andries K Nguyen CH Grierson DS 《Bioorganic & medicinal chemistry letters》2003,13(24):4309-4312
Building upon the potent anti-HIV-1 activities observed for the 3-dimethylamino-4-benzylpyridinone 2, and the corresponding 4-aryloxypyridinone analogue 3, a concise and efficient route to the 3-iodo-4-aryloxypyridinones 14a–c (IOPY's) was developed. This involved reaction of the 4-hydroxy substituted pyridinone 10 with the requisite dichloroiodobenzene reagent 11. IOPY compound 14c is active at IC50=1–45 nM against wild type HIV-1 and a panel of six major simple/double HIV mutant strains. 相似文献
45.
Raboisson P de Kock H Rosenquist A Nilsson M Salvador-Oden L Lin TI Roue N Ivanov V Wähling H Wickström K Hamelink E Edlund M Vrang L Vendeville S Van de Vreken W McGowan D Tahri A Hu L Boutton C Lenz O Delouvroy F Pille G Surleraux D Wigerinck P Samuelsson B Simmen K 《Bioorganic & medicinal chemistry letters》2008,18(17):4853-4858
SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamide (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics. 相似文献
46.
Naima Taqarort Abdelouahed Echairi Remi Chaussod Rachida Nouaim Hassan Boubaker Abdellah A. Benaoumar Elhassan Boudyach 《World journal of microbiology & biotechnology》2008,24(12):3031-3038
Epiphytic yeasts isolated from the surface of citrus fruits, harvested in several orchards in the Souss-Massa-Draa Valley,
Agadir, Morocco, were in vivo screened for antagonistic activity against Penicillium digitatum, the causal agent of green mold of citrus. From a total of 245 yeast strains assessed for their biocontrol activity against
P. digitatum, fifteen reduced the incidence of disease to less than 50%. The effectiveness of the best selected yeast strains showed that
Pichia anomala (YT73), Debaryomyces hansenii (YT22) and Hanseniaspora guilliermondii (YT13) were the most effective, with a reduction of green mold incidence from 65 to ~80%, compared to the control. The identification
of the fifteen selected yeast strains was carried out through an integrated approach including phenotypic and genotypic (sequencing
of D1/D2 domain of 26S rDNA encoding gene) methods. These 15 selected were identified as: H. guilliermondii, D. hansenii, H. uvarum and P. anomala. The study of the dynamics of two of the best strains, H. guilliermondii and D. hansenii, showed that these strains can grow rapidly, by approximately 2 log units, in citrus fruit wounds. Such rapid growth in wounds
indicates that these antagonist yeasts are excellent colonizers of citrus wounds and can thrive on citrus fruits as a substrate. 相似文献
47.
Ezzikouri S El Feydi AE Chafik A Afifi R El Kihal L Benazzouz M Hassar M Pineau P Benjelloun S 《Mutation research》2008,649(1-2):1-6
Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The main risk factors for its development are hepatitis B and C virus infections. Hepatitis B and C viruses induce chronic inflammation and oxidative stress that could predispose a cell to mutagenesis and proliferation. Manganese superoxide dismutase (MnSOD) catalyses the detoxification of free radicals, thus playing a crucial role in the protection against damage. A valine (Val) to alanine (Ala) substitution at amino acid 9, mapping within the mitochondrion-targeting sequence of the MnSOD gene, has been associated with an increased cancer risk. The aim of our study was to investigate a possible association of the Val/Ala-MnSOD polymorphism and HCC development in Moroccan patients. Genotypes were determined by means of PCR and RFLP analysis in 96 patients with HCC and 222 control subjects matched for age, sex, and ethnicity. Homozygous Ala/Ala carriers were 31% in the cases and 18% in the controls, which corresponds to an odds ratio (OR) of 2.89, with a 95% confidence interval (CI) of 1.47-5.68. Stratification into subgroups based on HCV infection status revealed an even more increased risk for homozygous Ala/Ala carriers with hepatitis C infection (38.2% in the cases versus 14.8% in the control subjects OR, 5.09; 95% CI, 1.76-14.66). Our findings provide further evidence of an association between the Ala-9Val MnSOD polymorphism and HCC occurrence in hepatitis C virus-infected Moroccan patients. 相似文献
48.
Dr. Jacques Frère Abdellah Benachour Madeleine Novel Georges Novel 《Current microbiology》1993,27(2):97-102
The replication region of pUCL22, the lactose-protease plasmid ofLactococcus lactis subsp.lactis (Lc. lactis) CNRZ270, was isolated on an 18-kbBamHI fragment, by cloning into pUCB300, anEscherichia coli vector encoding Emr, and selecting for Emr inLc. lactis MG1614. Subcloning and deletion analysis localized the replication region, namedRep22, on a 2.3-kb fragment. Replicons based on this region followed a theta-type mechanism of replication inLc. lactis. An internal 1251-bpDraI fragment ofRep22 used as a probe hybridized with numerous plasmids in bacteria from the generaLactococcus, Lactobacillus, andLeuconostoc. In some strains, two or three coresident plasmids hybridized with the probe in stringent conditions. It appears, therefore, that this family of theta-type replicons is widely distributed in lactic acid bacteria and contains several incompatibility groups. 相似文献
49.
Earth's biosphere is surrounded by magnetic fields that affect all living organisms. A plant's response to magnetic fields is displayed in terms of its seed's vigor, growth, and yield. Examining seed germination in such magnetic fields is the first step in the investigation of how magnetic fields might be used to enhance plant growth and maximize crop performance. In this study, salinity-sensitive Super Strain-B tomato seeds were primed with the northern and southern poles of neodymium magnets of 150, 200, and 250 mT. The magneto-primed seeds showed a significant increase in germination rate and speed, where the orientation of the magnet was identified as being crucial for germination rate and the orientation of seeds towards the magnet was shown to affect the germination speed. The primed plants exhibited enhanced growth characteristics, including longer shoots and roots, larger leaf area, more root hairs, higher water content, and more tolerance to salinity levels, up to 200 mM NaCl. All magneto-primed plants showed a significant decrease in chlorophyll content, continuous chlorophyll fluorescence yield (Ft), and quantum yield (QY). The salinity treatments decreased all chlorophyll parameters in control plants, significantly, but did not lower such parameters in magneto-primed tomatoes. The results of this study illustrate the positive effects of neodymium magnet on the growth and development of tomato plants in terms of their germination, growth, and salinity tolerance, and negatively affected the chlorophyll content in tomato leaves. © 2023 Bioelectromagnetics Society. 相似文献
50.
Cylindrospermopsin, a cyanobacterial guanidine alkaloid hepatotoxin and protein synthesis-inhibitor, was assayed for its effects on the germination of pollen from tobacco (Nicotiana tabacum cv Samsun NN). Pollen germination, measured by Alcian Blue dye-binding, was inhibited by cylindrospermopsin between 5 and 1000 microg ml(-1). As a protein synthesis-inhibitor, cylindrospermopsin did not inhibit pollen germination to the same extent as cycloheximide on a gravimetric basis, but significantly reduced the amount of (14)C-(U)-l-leucine labelling in pollen tubes. The inhibition of tobacco pollen germination may be amenable for development as a bioassay for cylindrospermopsin, although this would require a pre-concentration step for the monitoring of environmental samples. Implications of these observations for current spray-irrigation practices are discussed. 相似文献