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Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach 下载免费PDF全文
Karolina Słoczyńska Katarzyna Wójcik‐Pszczoła Vittorio Canale Paweł Żmudzki Paweł Zajdel Elżbieta Pękala 《Journal of biochemical and molecular toxicology》2018,32(5)
The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions. 相似文献
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Habitat fragmentation has often been implicated in the decline of many species. For habitat specialists and/or sedentary species, loss of habitat can result in population isolation and lead to negative genetic effects. However, factors other than fragmentation can often be important and also need to be considered when assessing the genetic structure of a species. We genotyped individuals from 13 populations of the cooperatively breeding Brown‐headed Nuthatch Sitta pusilla in Florida to test three alternative hypotheses regarding the effects that habitat fragmentation might have on genetic structure. A map of potential habitat developed from recent satellite imagery suggested that Brown‐headed Nuthatch populations in southern Florida occupied smaller and more isolated habitat patches (i.e. were more fragmented) than populations in northern Florida. We also genotyped individuals from a small, isolated Brown‐headed Nuthatch population on Grand Bahama Island. We found that populations associated with more fragmented habitat in southern Florida had lower allelic richness than populations in northern Florida (P = 0.02), although there were no differences in heterozygosity. Although pairwise estimates of FST were low overall, values among southern populations were generally higher than northern populations. Population assignment tests identified K = 3 clusters corresponding to a northern cluster, a southern cluster and a unique population in southeast Florida; using sampling localities as prior information revealed K = 7 clusters, with greater structure only among southern Florida populations. The Bahamas population showed moderate to high differentiation compared with Florida populations. Overall, our results suggest that fragmentation could affect gene flow in Brown‐headed Nuthatch populations and is likely to become more pronounced over time. 相似文献
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对中国云南西部和西北部分布的腋花扭柄花Streptopus simplex的4个居群进行了细胞学研究。生长在云南西北香格里拉县(原中甸县)碧塔海和小中甸冷杉林中的腋花扭柄花两个居群的体细胞染色体数目为2n=2x=18,而生长在高黎贡山的福贡县片马和贡山县的灌丛中的植物体细胞染色体数目则为2n=2x=14。2n=14为腋花扭柄花一个新的染色体数目,x=7为扭柄花属一个新的染色体基数。香格里拉碧塔海和小中甸两个居群的核型公式分别为2n=4m+8sm+4st和2n=8m+2sm+6st,染色体逐渐变小;贡山和福贡片马两个居群的核型公式分别为2n=14=4m+10sm和2n=14=7m+7sm,其中第一对中部着丝粒的染色体显著大于其余染色体。由于x=8是扭柄花属最常见的染色体基数,因此可认为x=8是腋花扭柄花的染色体原始基数,x=7的数目是衍生的;x=7居群染色体的一条大染色体可能是由x=8的染色体的两条st型染色体的着丝粒发生了罗伯逊易位而来。 相似文献
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研究了不同猕猴桃品种展叶孕蕾期自然感染溃疡病菌前后一年生枝条、叶片内过氧化物酶(POD)、多酚氧化酶(PPO)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、苯丙氨酸解氨酶(PAL)酶活性的变化情况.结果表明:感染溃疡病菌前后,抗病品种和感病品种枝条及成叶中防御酶系活性变化规律存在一定的差异.品种未受溃疡病菌感染时,一年生枝条、叶片中的POD、PPO、SOD、CAT酶活性抗病品种的酶活性均低于感病品种.品种自然感染溃疡病菌后,一年生枝条、叶片POD、PPO、SOD、CAT、PAL酶活性均升高,且酶活性的增加幅度是抗病品种中酶活提高倍数高于感病品种.而且这种增量在不同保护酶类以及不同组织部位是有差异的. 相似文献
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In vivo fluorescence imaging uses a sensitive camera to detect fluorescence emission from fluorophores in whole-body living small animals. To overcome the photon attenuation in living tissue, fluorophores with long emission at the near-infrared (NIR) region are generally preferred, including widely used small indocarbocyanine dyes. The list of NIR probes continues to grow with the recent addition of fluorescent organic, inorganic and biological nanoparticles. Recent advances in imaging strategies and reporter techniques for in vivo fluorescence imaging include novel approaches to improve the specificity and affinity of the probes and to modulate and amplify the signal at target sites for enhanced sensitivity. Further emerging developments are aiming to achieve high-resolution, multimodality and lifetime-based in vivo fluorescence imaging. 相似文献