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951.
Peiro G Alary J Cravedi JP Rathahao E Steghens JP Guéraud F 《BioFactors (Oxford, England)》2005,24(1-4):89-96
The objective of our study was to compare the information obtained through the use of three different urinary biomarkers of lipoperoxidation during the time course of a bromotrichloromethane (BrCCl3) induced oxidative stress in rats. These biomarkers were malondialdehyde (MDA) measured by LC/MS after derivatization, the isoprostane 8-iso-PGF2alpha measured by enzyme immunoassay and 1,4-dihydroxynonene mercapturic acid (DHN-MA), the major 4-hydroxynonenal urinary metabolite [1], measured by LC-MS. Male Wistar rats received a single dose of 100 microL/kg BrCCl3 per os and lipid peroxidation was estimated every day for a 4-day-period after treatment. MDA, 8-iso-PGF2alpha and DHN-MA significantly increased in response to BrCCl3 treatment for this period of time, and DHN-MA showed the main increase during the 24-48 h period after treatment. 相似文献
952.
Conventional organic fluorophores suffer from poor photo stability, narrow absorption spectra and broad emission spectra. Semiconductor nanocrystals, however, are highly photo-stable with broad absorption spectra and narrow size-tunable emission spectra. Recent advances in the synthesis of these materials have resulted in the generation of bright, sensitive, extremely photo-stable and biocompatible semiconductor fluorophores. Commercial availability facilitates their application in a variety of unprecedented biological experiments, including multiplexed cellular imaging, long-term in vitro and in vivo labeling, deep tissue structure mapping and single particle investigation of dynamic cellular processes. Semiconductor nanocrystals are one of the first examples of nanotechnology enabling a new class of biomedical applications. 相似文献
953.
Small reducing and linear oligo-beta-(1,3)-glucans, which are able to act as phytoallexin elicitors or as immunostimulating agents in anticancer therapy, were synthesized according to an iterative strategy that involved a unique key monosaccharidic donor. To avoid anomeric mixtures, the reducing entity of the target oligomers was first locked with benzyl alcohol and further selective deprotection of the 3-OH with DDQ afforded the desired building block as an acceptor. The latter was then used in a second cycle of glycosylation/deprotection to afford the desired disaccharide, and successive reiterations of this process provided the desired oligomers. Unusual conformational behaviors were observed by standard NMR sequences and supported by NOESY studies. Finally, removal of protecting groups afforded free tri-, tetra-, and pentaglucosides in good overall yields. Two oligosaccharides representing linear laminaritetraose and laminaripentaose were compared to the recently described beta-(1,3)-glucan phycarine. Following an intraperitoneal injection, the influx of monocytes and granulocytes into the blood and macrophages into the peritoneal cavity was comparable to that caused by phycarine. Similarly, both oligosaccharides stimulated phagocytic activity of granulocytes and macrophages. Using ELISA, we also demonstrated a significant stimulation of secretion of IL-1beta. Together these results suggest that the synthetic oligosaccharides have similar stimulatory effects as natural beta-(1,3)-glucans. 相似文献
954.
Zirihi GN Grellier P Guédé-Guina F Bodo B Mambu L 《Bioorganic & medicinal chemistry letters》2005,15(10):2637-2640
Bioassay-guided fractionation of the EtOH extract of the stem bark of Funtumia elastica resulted in the isolation of four steroidal alkaloids, holarrhetine (1), conessine (2), holarrhesine (3) and isoconessimine (4). Their structures were determined on the basis of 1D- and 2D-NMR techniques and mass spectrometry. Compounds 1-4 exhibited in vitro antiplasmodial activity against the chloroquine-resistant strain FcB1 of Plasmodium falciparum with IC50 values ranging from 0.97 to 3.39 microM. They showed weak cytotoxicity against a rat cell line L-6 with IC50 values ranging from 5.13 to 36.55 microM. 相似文献
955.
Kreusch A Han S Brinker A Zhou V Choi HS He Y Lesley SA Caldwell J Gu XJ 《Bioorganic & medicinal chemistry letters》2005,15(5):1475-1478
A series of dihydroxyphenylpyrazole compounds were identified as a unique class of reversible Hsp90 inhibitors. The crystal structures for two of the identified compounds complexed with the N-terminal ATP binding domain of human Hsp90alpha were determined. The dihydroxyphenyl ring of the compounds fits deeply into the adenine binding pocket with the C2 hydroxyl group forming a direct hydrogen bond with the side chain of Asp93. The pyrazole ring forms hydrogen bonds to the backbone carbonyl of Gly97, the hydroxyl group of Thr184 and to a water molecule, which is present in all of the published HSP90 structures. One of the identified compounds (G3130) demonstrated cellular activities (in Her-2 degradation and activation of Hsp70 promoter) consistent with the inhibition of cellular Hsp90 functions. 相似文献
956.
Shue HJ Chen X Shih NY Blythin DJ Paliwal S Lin L Gu D Schwerdt JH Shah S Reichard GA Piwinski JJ Duffy RA Lachowicz JE Coffin VL Liu F Nomeir AA Morgan CA Varty GB 《Bioorganic & medicinal chemistry letters》2005,15(17):3896-3899
A series of novel five- and six-membered ring urea derivatives have been described as potent and selective NK1 receptor antagonists. Several compounds in this series exhibited good oral activity and brain penetration. Syntheses of these compounds are also described herein. 相似文献
957.
Li Q Woods KW Wang W Lin NH Claiborne A Gu WZ Cohen J Stoll VS Hutchins C Frost D Rosenberg SH Sham HL 《Bioorganic & medicinal chemistry letters》2005,15(8):2033-2039
Beginning with the structure of tipifarnib (1), a series of inhibitors of FTase have been synthesized by transposition of the D-ring to the imidazole and subsequent modification of the 2-quinolone motif. The compounds in the new series may be achiral and have structural features that allow for analogs that are difficult or impossible to make in the tertiary carbon-based tipifarnib series. The most potent compound (4d) is 4 times more active in vitro against FTase than tipifarnib. 相似文献
958.
Gustin DJ Sehon CA Wei J Cai H Meduna SP Khatuya H Sun S Gu Y Jiang W Thurmond RL Karlsson L Edwards JP 《Bioorganic & medicinal chemistry letters》2005,15(6):1687-1691
A novel series of competitive, reversible cathepsin S (CatS) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of CatS inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. 相似文献
959.
In this study, we identified lymphocytes and MHC class II positive (MHC-II+) cells in the reproductive tract of female rabbits both before and after ovulation. CD43+ T cells were frequently present in the mucosa of the oviduct, cervix, and vagina, but far fewer positive cells were seen in the endometrium. The induction of ovulation did not change the cell density in these regions. KEN-5+ T cells and MHC-II+ cells were also frequently seen in the mucosa of the oviduct, cervix, and vagina both before and after ovulation. However, in the uterus, there were very few positive cells before ovulation, but the number increased dramatically after ovulation. Associated with the increase of KEN-5+ T cells, IL-2 mRNA expression in the uterus also increased after ovulation, suggesting that the uterus experienced an increase of T-cell activation. IgM- and IgA-positive B cells were not commonly seen in the reproductive tract and the induction of ovulation did not alter this. Our results suggest that the reproductive tract of female rabbits has the capacity to mount an immune response and that the immune cell distribution of the rabbit reproductive tract has some distinctive features compared with that found in other species. 相似文献
960.