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331.
Sherida L. Johnson Li-Hsing Chen Elisa Barile Aras Emdadi Mojgan Sabet Hongbin Yuan Jun Wei Donald Guiney Maurizio Pellecchia 《Bioorganic & medicinal chemistry》2009,17(9):3352-3368
We report on the identification of a novel small molecule inhibitor of anthrax lethal factor using a high-throughput screening approach. Guided by molecular docking studies, we carried out structure–activity relationship (SAR) studies and evaluated activity and selectivity of most promising compounds in in vitro enzyme inhibition assays and cellular assays. Selected compounds were further analyzed for their in vitro ADME properties, which allowed us to select two compounds for further preliminary in vivo efficacy studies. The data provided represents the basis for further pharmacology and medicinal chemistry optimizations that could result in novel anti-anthrax therapies. 相似文献
332.
Romagnoli R Baraldi PG Moorman AR Iaconinoto MA Carrion MD Cara CL Tabrizi MA Preti D Fruttarolo F Baker SP Varani K Borea PA 《Bioorganic & medicinal chemistry letters》2006,16(21):5530-5533
The microwave-assisted aromatization method has been used for the synthesis of a series of novel thieno[2,3-c]pyridines. This rapid method produces compounds in good yield within minutes in comparison with conventional heating method. The synthesized molecules have been evaluated as a potential new series of allosteric enhancers acting at the adenosine A(1) receptor. In a functional assay, one compound (3h) showed activity comparable with that of reference compound PD 81,723. 相似文献
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334.
The objective of the present study was to estimate genetic parameters for post-weaning traits in Kermani sheep. Traits were included 6-month weight (6MW), 9-month weight (9MW), yearling weight (YW), greasy fleece weight at first shearing (GFW) and greasy fleece weights at various shearings (RFW). Data and pedigree information used in this research were collected at Breeding Station of Kermani sheep during 1993–2004. Genetic parameters were estimated with single- and multi-traits analysis using restricted maximum likelihood (REML) procedures, under animal models. Log likelihood ratio test indicated the most appropriate model for 6MW and 9MW should included direct additive genetic effects as well as maternal permanent environmental effects. However the most appropriate model for YW and GFW had only the direct additive genetic effects. The effects of sex, age of dam and year of birth were significant on body weight traits (P < 0.01). GFW was influenced significantly by sex and year of birth (P < 0.01) but was not affected by age of dam (P > 0.05). Type of birth was no significant effect on studied traits (P > 0.05). Also, the age of lamb at weighing time was a significant influence on 6MW, 9MW and YW. Direct heritability estimates for 6MW, 9MW, YW and GFW were 0.32, 0.03, 0.15 and 0.15, respectively. Maternal permanent environmental estimates of 0.09 were obtained for 6MW and 9MW. Genetic correlation estimates between mentioned traits ranged from 0.51 to 0.99. Phenotypic correlations were generally lower than those of genetic correlation and varied from 0.05 to 0.79 for various traits. The environmental correlations estimates between GFW with growth traits were low, but between other traits were positive and high, ranged from 0.54 to 0.72. The value of repeatability estimated for greasy fleece weight was 0.22. 相似文献
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336.
Bayat A 《Plastic and reconstructive surgery》2003,111(1):501-502
337.
Baraldi PG Bovero A Fruttarolo F Romagnoli R Tabrizi MA Preti D Varani K Borea PA Moorman AR 《Bioorganic & medicinal chemistry》2003,11(19):4161-4169
New A(3) adenosine receptor antagonists were synthesized and tested at human adenosine receptor subtypes. An advanced synthetic strategy permitted us to obtain a large amount of the key intermediate 5 that was then submitted to alkylation procedures in order to obtain the derivatives 6-8. These compounds were then functionalised into ureas at the 5-position (compounds 9-11, 18 and 19) to evaluate their affinity and selectivity versus hA(3) adenosine receptor subtype; in particular, compounds 18 and 19 displayed a value of affinity of 4.9 and 1.3 nM, respectively. Starting from 5, the synthetic methodologies employed permitted us to perform a rapid and a convenient divergent synthesis. A further improvement allowed the regioselective preparation of the N(8)-substituted compound 7. This method could be used as an helpful general procedure for the design of novel A(3) adenosine receptor antagonists without the difficulty of separating the N(8)-substituted pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines from the corresponding N(7)-isomers. 相似文献
338.
Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts 总被引:76,自引:0,他引:76
Transplantation of adult bone marrow-derived mesenchymal stem cells has been proposed as a strategy for cardiac repair following myocardial damage. However, poor cell viability associated with transplantation has limited the reparative capacity of these cells in vivo. In this study, we genetically engineered rat mesenchymal stem cells using ex vivo retroviral transduction to overexpress the prosurvival gene Akt1 (encoding the Akt protein). Transplantation of 5 x 10(6) cells overexpressing Akt into the ischemic rat myocardium inhibited the process of cardiac remodeling by reducing intramyocardial inflammation, collagen deposition and cardiac myocyte hypertrophy, regenerated 80-90% of lost myocardial volume, and completely normalized systolic and diastolic cardiac function. These observed effects were dose (cell number) dependent. Mesenchymal stem cells transduced with Akt1 restored fourfold greater myocardial volume than equal numbers of cells transduced with the reporter gene lacZ. Thus, mesenchymal stem cells genetically enhanced with Akt1 can repair infarcted myocardium, prevent remodeling and nearly normalize cardiac performance. 相似文献
339.