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1.
Ehsan Ullah Mughal Amina Sadiq Shahzad Murtaza Hummera Rafique Muhammad Naveed Zafar Tauqeer Riaz Bilal Ahmad Khan Abdul Hameed Khalid Mohammed Khan 《Bioorganic & medicinal chemistry》2017,25(1):100-106
The present study describes efficient and facile syntheses of varyingly substituted 3-thioaurones from the corresponding 3-oxoaurones using Lawesson’s reagent and phosphorous pentasulfide. In comparison, the latter methodology was proved more convenient, giving higher yields and required short and simple methodology. The structures of synthetic compounds were unambiguously elucidated by IR, MS and NMR spectroscopy. All synthetic compounds were screened for their inhibitory potential against in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Molecular docking studies were also performed in order to examine their binding interactions with AChE and BChE human proteins. Both studies revealed that some of these compounds were found to be good inhibitors against AChE and BChE. 相似文献
2.
以中国科学院新疆巴音布鲁克草原生态站为依托,于2010年5月—2011年10月利用静态箱-气相色谱法对短期禁牧(2005年围封)、长期禁牧(1984年围封)和自由放牧(冬季放牧)3种草地的CO2、CH4、N2O气体通量进行了野外连续试验研究。结果表明:新疆天山高寒草原对CO2,CH4和N2O通量表现出明显的季节排放特点。在植物的生长季(5—10月),新疆天山高寒短期禁牧、长期禁牧和自由放牧草原的CO2通量平均值分别为:(89.8±49.3)、(52.8±28.7)、(57.0±30.7)mg·m-2·h-1,CH4通量平均值分别为:(-66.3±21.3)、(-104.5±32.8)、(-103.0±39.0)μg·m-2·h-1,N2O通量平均值分别为:(21.2±11.8)、(13.6±6.9)、(13.2±6.2)μg·m-2·h-1;短期禁牧草原与长期禁牧和自由放牧草原CH4平均通量具有显著性差异(P0.05),但CO2和N2O差异不显著(P0.05)。在植物的非生长季(11月—翌年4月),新疆天山高寒短期禁牧、长期禁牧以及自由放牧草原的3种温室气体的通量较低且差异均不显著。 相似文献
3.
Sébastien L. Degorce Rana Anjum Keith S. Dillman Lisa Drew Sam D. Groombridge Christopher T. Halsall Eva M. Lenz Nicola A. Lindsay Michele F. Mayo Jennifer H. Pink Graeme R. Robb James S. Scott Stephen Stokes Yafeng Xue 《Bioorganic & medicinal chemistry》2018,26(4):913-924
We have developed a series of orally efficacious IRAK4 inhibitors, based on a scaffold hopping strategy and using rational structure based design. Efforts to tackle low permeability and high efflux in our previously reported pyrrolopyrimidine series (Scott et al., 2017) led to the identification of pyrrolotriazines which contained one less formal hydrogen bond donor and were intrinsically more lipophilic. Further optimisation of substituents on this pyrrolotriazine core culminated with the discovery of 30 as a promising in vivo probe to assess the potential of IRAK4 inhibition for the treatment of MyD88 mutant DLBCL in combination with a BTK inhibitor. When tested in an ABC-DLBCL model with a dual MyD88/CD79 mutation (OCI-LY10), 30 demonstrated tumour regressions in combination with ibrutinib. 相似文献
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5.
Xiao Zhang Xixin He Qiuhe Chen Junfeng Lu Simona Rapposelli Rongbiao Pi 《Bioorganic & medicinal chemistry》2018,26(3):543-550
Alzheimer’s disease (AD), a complex chronic progressive central nervous system degenerative disease and a public health problem of the world, often characters cognitive dysfunction accompaning aggression and depression, and may lead to death. More attentions should be paid on it because there is no modified strategy against AD till now. AD is featured with the loss of cholinergic neurons, the amyloid-beta peptide (Aβ) plaques and the neurofibrillary tangles and several hypotheses were established to explain the pathogenesis of AD. Hydroxycinnamic acids, including caffeic acid (CA) and ferulic acid (FA) are widely distributed in natural plants and fruits. CA and FA exert various pharmacological activities, including anti-inflammatory, antioxidant, neuroprotection, anti-amyloid aggregation and so on. All these pharmacological activities are associated with the treatment of AD. Here we summarized the pharmacological activities of CA and FA, and their hybrids as multi-target-directed ligands (MTDLs) against AD. The future application of CA and FA was also discussed, hoping to provide beneficial information for the development of CA- and FA-based MTDLs against AD. 相似文献
6.
The precise demarcation between earlywood and latewood is important for the detailed analysis of intra-annual tree ring features. Different techniques based on visual assessment, wood anatomy analysis and X-ray densitometry have been developed and are currently used for this purpose. Depending on the chosen method, tree species and environmental conditions, the results can significantly vary. Thus, it is important to determine the technique optimal for a particular research. Here, we investigated Norway spruce (Picea abies) tree rings to examine the agreement among the following demarcation methods: (1) direct visual assessment, (2) Mork’s index (anatomical definition of the transition from earlywood to latewood based on cell wall-lumen ratio) and (3) fixed and floating density thresholds applied to intra-ring density profiles. The aim was to modify both the Mork’s criterion and density thresholds on the basis of reference values given by visual identification of earlywood/latewood transition. A total of 231 tree rings were analysed by all methods. Our results showed that the usage of floating threshold (defined for each ring separately based on density profiles) is more reliable in comparison with fixed threshold (the same threshold value used for all tree rings and samples). Statistical analysis revealed the best correspondence between visual identification of earlywood/latewood transition and demarcation based on the standard Mork’s index and the floating density threshold derived as 80 % of maximum latewood density. In terms of Mork’s index calibration, the results showed that to determine latewood cells in Norway spruce trees growing in temperate conditions, it is sufficient to use an index value equal to 0.83. The results are applicable for the studied spruce population growing in a temperate climate. The methodology itself, however, is universal and can help to calibrate criteria for earlywood-latewood demarcation under specific conditions. 相似文献
7.
Subhadip Hajra Abhishek Basu Somnath Singha Roy Arup Ranjan Patra Sudin Bhattacharya 《Free radical research》2017,51(9-10):812-827
The most crucial complication related to doxorubicin (DOX) therapy is nonspecific cytotoxic effect on healthy normal cells. The clinical use of this broad-spectrum chemotherapeutic agent is restricted due to development of severe form of cardiotoxicity, myelosuppression, and genotoxicity which interfere with therapeutic schedule, compromise treatment outcome and may lead to secondary malignancy. 3,3′-diindolylmethane (DIM) is a naturally occurring plant alkaloid formed by the hydrolysis of indolylmethyl glucosinolate (glucobrassicin). Therefore, the present study was undertaken to investigate the protective role of DIM against DOX-induced toxicity in mice. DOX was administered (5?mg/kg b.w., i.p.) and DIM was administered (25?mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results showed that DIM significantly attenuated DOX-induced oxidative stress in the cardiac tissues by reducing the levels of free radicals and lipid peroxidation, and by enhancing the level of glutathione (reduced) and the activity of antioxidant enzymes. The chemoprotective potential of DIM was confirmed by histopathological evaluation of heart and bone marrow niche. Moreover, DIM considerably mitigated DOX-induced clastogenicity, DNA damage, apoptosis, and myeloid hyperplasia in bone marrow niche. In addition, oral administration of DIM significantly (p?.05) stimulated the Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, HO-1, NQO1, and glutathione-S-transferase (GST). In connection with that, DIM significantly attenuated DOX-induced apoptosis by upregulation of Bcl-2 expression and downregulation of Bax and caspase-3 expression. Thus, this study suggests that DIM has promising chemoprotective efficacy against DOX-induced toxicity and indicates its future use as an adjuvant in chemotherapy. 相似文献
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9.
《Geobios》2014,47(6):389-401
The conodont faunas of Tournaisian shallow-water carbonates from central Guangxi are described mainly for biostratigraphic purposes. A complete series of samples was collected from the Long’an and Du’an formations in the Long’an section. These formations are characterized by lime-mudstone, skeletal and peloidal wackestone, packstone and grainstone with typical shallow-water biota. Overall, these samples produced 809 identifiable Pl elements, belonging to 50 species in 11 genera, of which one species and one subspecies are new. The fauna enables the establishment of seven biozones (in ascending order): Polygnathus spicatus, Siphonodella homosimplex, S. sinensis, S. dasaibaensis, Polygnathus communis carina Acme, Gnathodus cuneiformis, and P. communis porcatus zones. Based on these new collections from central Guangxi and on data from the literature, a conflated Tournaisian conodont zonation is proposed for shallow-water successions in South China. Most of the conodont zones correlate well with their counterparts recognized in Western Europe, which may be of greater significance in stratigraphic correlation than previously thought. 相似文献
10.
The brain is very sensitive to changes in redox status; thus maintaining redox homeostasis in the brain is critical for the prevention of accumulating oxidative damage. Aging is the primary risk factor for developing neurodegenerative diseases. In addition to age, genetic and environmental risk factors have also been associated with disease development. The primary reactive insults associated with the aging process are a result of oxidative stress (OS) and nitrosative stress (NS). Markers of increased oxidative stress, protein and DNA modification, inflammation, and dysfunctional proteostasis have all been implicated in contributing to the progression of neurodegeneration. The ability of the cell to combat OS/NS and maintain a clearance mechanism for misfolded aggregating proteins determines whether or not it will survive. A critical pathway in this regard is the Nrf2 (nuclear factor erythroid 2-related factor 2)- antioxidant response element (ARE) pathway. Nrf2 activation has been shown to mitigate a number of pathologic mechanisms associated with Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. This review will focus on the role of Nrf2 in these diseases and the potential for Nrf2 activation to attenuate disease progression. 相似文献