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211.
Serdar Ünlü Erden Banoglu Shigeru Ito Tokihiro Niiya Gökçen Eren Berna Ökçelik 《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):351-361
In a search for novel compounds with analgesic and anti-inflammatory activity, a series of regioisomeric 1-(3-pyridazinyl)-3-arylpyrazole (5a–f, 6a–f) and 1-(3-pyridazinyl)-5-arylpyrazole (7a–f, 8a–f) derivatives were synthesized. The structure of these regioisomers was confirmed by spectral techniques. The compounds were preliminarily screened at 8 μM concentration for their inhibitory activity against cyclooxygenase enzymes, COX-1 and COX-2, using a human whole blood test. The tested derivatives showed inhibitory activity for both enzymes and are worthy of further investigation for developing better leads. 相似文献
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213.
Michelle M. Merrigan Anilrudh Venugopal Jennifer L. Roxas Farhan Anwar Michael J. Mallozzi Bryan A. P. Roxas Dale N. Gerding V. K. Viswanathan Gayatri Vedantam 《PloS one》2013,8(11)
Clostridium difficile is a leading cause of antibiotic-associated diarrhea, and a significant etiologic agent of healthcare-associated infections. The mechanisms of attachment and host colonization of C. difficile are not well defined. We hypothesize that non-toxin bacterial factors, especially those facilitating the interaction of C. difficile with the host gut, contribute to the initiation of C. difficile infection. In this work, we optimized a completely anaerobic, quantitative, epithelial-cell adherence assay for vegetative C. difficile cells, determined adherence proficiency under multiple conditions, and investigated C. difficile surface protein variation via immunological and DNA sequencing approaches focused on Surface-Layer Protein A (SlpA). In total, thirty-six epidemic-associated and non-epidemic associated C. difficile clinical isolates were tested in this study, and displayed intra- and inter-clade differences in attachment that were unrelated to toxin production. SlpA was a major contributor to bacterial adherence, and individual subunits of the protein (varying in sequence between strains) mediated host-cell attachment to different extents. Pre-treatment of host cells with crude or purified SlpA subunits, or incubation of vegetative bacteria with anti-SlpA antisera significantly reduced C. difficile attachment. SlpA-mediated adherence-interference correlated with the attachment efficiency of the strain from which the protein was derived, with maximal blockage observed when SlpA was derived from highly adherent strains. In addition, SlpA-containing preparations from a non-toxigenic strain effectively blocked adherence of a phylogenetically distant, epidemic-associated strain, and vice-versa. Taken together, these results suggest that SlpA plays a major role in C. difficile infection, and that it may represent an attractive target for interventions aimed at abrogating gut colonization by this pathogen. 相似文献
214.
Oktay Talaz Hüseyin Çavdar Serdar Durdagi Hacer Azak Deniz Ekinci 《Bioorganic & medicinal chemistry》2013,21(6):1477-1482
Several 1,4-bis(indolin-1-ylmethyl)benzene-based compounds containing substituents such as five, six and seven cyclic derivatives on indeno part (9a–c) were prepared and tested against two members of the pH regulatory enzyme family, carbonic anhydrase (CA). The inhibitory potencies of the compounds at the human isoforms hCA I and hCA II targets were analyzed and KI values were calculated. KI values of compounds for hCA I and hCA II human isozymes were measured in the range of 39.3–42.6 μM and 0.17–0.29 μM, respectively. The structurally related compound indole was also tested in order to understand the structure–activity relationship. Most of the compounds showed good CA inhibitory efficacy. In silico docking studies of these derivatives within hCA I and II were also carried out and results are supported the kinetic assays. 相似文献
215.
216.
Mustafeez Mujtaba Babar Muhammad Suleman Riaz Najam-us-Sahar Sadaf Zaidi Farhan Afzal Muhammad Sabir Farooq 《Journal of industrial microbiology & biotechnology》2013,40(6):625-632
The global availability of a therapeutically effective influenza virus vaccine during a pandemic remains a major challenge for the biopharmaceutical industry. Long production time, coupled with decreased supply of embryonated chicken eggs (ECE), significantly affects the conventional vaccine production. Transformed cell lines have attained regulatory approvals for vaccine production. Based on the fact that the avian influenza virus would infect the cells derived from its natural host, the viral growth characteristics were studied on chicken embryo-derived primary cell cultures. The viral propagation was determined on avian origin primary cell cultures, transformed mammalian cell lines, and in ECE. A comparison was made between these systems by utilizing various cell culture-based assays. In-vitro substrate susceptibility and viral infection characteristics were evaluated by performing hemagglutination assay (HA), 50 % tissue culture infectious dose (TCID50) and monitoring of cytopathic effects (CPE) caused by the virus. The primary cell culture developed from chicken embryos showed stable growth characteristics with no contamination. HA, TCID50, and CPE exhibited that these cell systems were permissive to viral infection, yielding 2–10 times higher viral titer as compared to mammalian cell lines. Though the viral output from the ECE was equivalent to the chicken cell culture, the time period for achieving it was decreased to half. Some of the prerequisites of inactivated influenza virus vaccine production include generation of higher vial titer, independence from exogenous sources, and decrease in the production time lines. Based on the tests, it can be concluded that chicken embryo primary cell culture addresses these issues and can serve as a potential alternative for influenza virus vaccine production. 相似文献
217.
Abstract The sex genetic determinants of the dioecious species Asparagus offcinalis are codified on the chromosome pair n. 5 and inherited as a monomendelian trait; since the dominant alleal controls the development of androecium, the males are heterozygous and the female homozygous. The male plants of asparagus are know to be superiour respect to the female ones for important yield components, therefore one objectiv of the breeding is the synthesis of all-male hybrids. That is possible by crossing female plants (m/m) with male plaits (M/M) homozygous for sex pair chromosome. The synthes of such kind of males by selfing the rare andromonoecious plants, involves several problems which can be overcome by using the in vitro anther culture technique. At our Institute this technique has been sistematically applied during the last twenty years and allowed to regenerate doubled haploid clones which were evaluated in the field for a minimum period of four years. The best male and female clones were then utilized as parents of all-male F1 hybrids. Following omparative varietal trials in different location for several years, the best F1 all-mal hybrids were identified and released to private seed companies for the production of commercial seed. 相似文献
218.
Uda Y Poh YC Chowdhury F Wu DC Tanaka TS Sato M Wang N 《Biochemical and biophysical research communications》2011,(2):396-400
Increasing evidence suggests that mechanical factors play a critical role in fate decisions of stem cells. Recently we have demonstrated that a local force applied via Arg-Gly-Asp (RGD) peptides coated magnetic beads to mouse embryonic stem (ES) cells increases cell spreading and cell stiffness and decreases Oct3/4 (Pou5f1) gene expression. However, it is not clear whether the effects of the applied stress on these functions of ES cells can be extended to natural extracellular matrix proteins or cell–cell adhesion molecules. Here we show that a local cyclic shear force applied via fibronectin or laminin to integrin receptors increased cell spreading and stiffness, downregulated Oct3/4 gene expression, and decreased cell proliferation rate. In contrast, the same cyclic force applied via cell–cell adhesion molecule E-cadherin (Cdh1) had no effects on cell spreading, Oct3/4 gene expression, and the self-renewal of mouse ES cells, but induced significant cell stiffening. Our findings demonstrate that biological responses of ES cells to force applied via integrins are different from those to force via E-cadherin, suggesting that mechanical forces might play different roles in different force transduction pathways to shape early embryogenesis. 相似文献
219.
Biological ion channels rely on a multi-ion transport mechanism for fast yet selective permeation of ions. The crystal structure of the KcsA potassium channel provided the first microscopic picture of this process. A similar mechanism is assumed to operate in all potassium channels, but the validity of this assumption has not been well investigated. Here, we examine the energetics of ion permeation in Shaker Kv1.2 and KcsA channels, which exemplify the six-transmembrane voltage-gated and two-transmembrane inward-rectifier channels. We study the feasibility of binding a third ion to the filter and the concerted motion of ions in the channel by constructing the potential of mean force for K+ ions in various configurations. For both channels, we find that a pair of K+ ions can move almost freely within the filter, but a relatively large free-energy barrier hinders the K+ ion from stepping outside the filter. We discuss the effect of the CMAP dihedral energy correction that was recently incorporated into the CHARMM force field on ion permeation dynamics. 相似文献
220.
Vuilleumier S Nadalig T Ul Haque MF Magdelenat G Lajus A Roselli S Muller EE Gruffaz C Barbe V Médigue C Bringel F 《Journal of bacteriology》2011,193(18):5035-5036
Hyphomicrobium sp. strain MC1 is an aerobic methylotroph originally isolated from industrial sewage. This prosthecate bacterium was the first strain reported to grow with chloromethane as the sole carbon and energy source. Its genome, consisting of a single 4.76-Mb chromosome, is the first for a chloromethane-degrading bacterium to be formally reported. 相似文献