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221.
Kai Cheng Shiyu Li Xiao Lv Yongbin Tian Haiyan Kong Xufeng Huang Yajun Duan Jihong Han Zhouling Xie Chenzhong Liao 《Bioorganic & medicinal chemistry letters》2019,29(8):1012-1018
Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems. 相似文献
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Jiangying Cao Jie Zang Xiujie Kong Chunlong Zhao Ting Chen Yingying Ran Hang Dong Wenfang Xu Yingjie Zhang 《Bioorganic & medicinal chemistry》2019,27(6):978-990
Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model. 相似文献
225.
Synthesis and biological evaluation of BMS-986120 and its deuterated derivatives as PAR4 antagonists
Panpan Chen Shenhong Ren Hangyu Song Cai Chen Fangjun Chen Qinglong Xu Yi Kong Hongbin Sun 《Bioorganic & medicinal chemistry》2019,27(1):116-124
BMS-986120 is a PAR4 antagonist that is being investigated as an antiplatelet agent in phase I clinical trial. An improved synthesis of BMS-986120 has been developed. Based on the novel synthetic approach to BMS-986120, a series of deuterated derivatives of BMS-986120 have been synthesized and biologically evaluated to search for more potent antiplatelet agents. The in vitro antiplatelet assay by turbidimetry demonstrated that PC-2 and PC-6 had IC50 values of 6.30?nM and 6.97?nM, respectively, versus BMS-986120 with an IC50 of 7.80?nM. The result of in vitro metabolic stability study showed that all of the deuterated compounds had similar half-life (T1/2) and intrinsic clearance (Clint) in comparison with BMS-986120. Further probing the metabolic profile of BMS-986120 is worth being conducted. 相似文献
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Ting-Gang Li Bao-Li Wang Chun-Mei Yin Dan-Dan Zhang Dan Wang Jian Song Lei Zhou Zhi-Qiang Kong Steven J. Klosterman Jun-Jiao Li Sabiu Adamu Ting-Li Liu Krishna V. Subbarao Jie-Yin Chen Xiao-Feng Dai 《Molecular Plant Pathology》2019,20(6):857-876
Improving genetic resistance is a preferred method to manage Verticillium wilt of cotton and other hosts. Identifying host resistance is difficult because of the dearth of resistance genes against this pathogen. Previously, a novel candidate gene involved in Verticillium wilt resistance was identified by a genome-wide association study using a panel of Gossypium hirsutum accessions. In this study, we cloned the candidate resistance gene from cotton that encodes a protein sharing homology with the TIR-NBS-LRR receptor-like defence protein DSC1 in Arabidopsis thaliana (hereafter named GhDSC1). GhDSC1 expressed at higher levels in response to Verticillium wilt and jasmonic acid (JA) treatment in resistant cotton cultivars as compared to susceptible cultivars and its product was localized to nucleus. The transfer of GhDSC1 to Arabidopsis conferred Verticillium resistance in an A. thaliana dsc1 mutant. This resistance response was associated with reactive oxygen species (ROS) accumulation and increased expression of JA-signalling-related genes. Furthermore, the expression of GhDSC1 in response to Verticillium wilt and JA signalling in A. thaliana displayed expression patterns similar to GhCAMTA3 in cotton under identical conditions, suggesting a coordinated DSC1 and CAMTA3 response in A. thaliana to Verticillium wilt. Analyses of GhDSC1 sequence polymorphism revealed a single nucleotide polymorphism (SNP) difference between resistant and susceptible cotton accessions, within the P-loop motif encoded by GhDSC1. This SNP difference causes ineffective activation of defence response in susceptible cultivars. These results demonstrated that GhDSC1 confers Verticillium resistance in the model plant system of A. thaliana, and therefore represents a suitable candidate for the genetic engineering of Verticillium wilt resistance in cotton. 相似文献
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通过盆栽试验,评价栎属植物在铅锌尾矿中的生长响应及植被恢复前景.分析比较了覆瓦栎、猩红栎、樱皮栎、舒玛栎和白栎5种栎树幼苗在铅锌矿砂中生长30个月后的生物量、根系形态及其对营养元素和重金属的吸收及转移特征.结果表明: 5种栎树在矿砂中均能生长,其中,猩红栎和白栎的生物量较对照有下降趋势,其他3种栎树的生长与对照相比无显著差异;栎树根系生物量均较对照有不同程度增加(猩红栎除外),且仅猩红栎侧根形态学参数较对照有所减少.重金属胁迫下,栎树根系和茎中营养元素浓度较对照无显著变化.5种栎树体内重金属浓度均较低,且其生物富集系数和转移系数均小于1.但樱皮栎叶片和茎中Cd浓度分别为22.4和15.1 mg·kg-1,转移系数为2.3,显著高于其他4种栎树.除猩红栎以外,其他参试栎树均可作为有潜力的污染土壤修复树种.其中舒玛栎的耐性较高、生物富集系数和转移系数较低,是适合在尾矿区造林和生态修复的优选树种. 相似文献
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基于多源遥感数据的植物物种分类与识别: 研究进展与展望 总被引:2,自引:0,他引:2
物种分类与识别是生物多样性监测的基础, 明确物种的类别及其分布是解决几乎所有生态学问题的前提。为深入了解基于多源遥感数据的植物物种分类与识别相关研究的发展现状和存在的问题, 本文对2000年以来该领域的研究进行了总结分析, 发现: 当前大多数研究集中在欧洲和北美地区的温带或北方森林以及南非的热带稀树草原; 使用最多的遥感数据是机载高光谱数据, 而激光雷达作为补充数据, 通过单木分割及提供单木的三维垂直结构信息, 显著提高了分类精度; 支持向量机和随机森林作为应用最广的非参数分类算法, 平均分类精度达80%; 随着计算机技术及机器学习领域的不断成熟, 人工神经网络在物种识别领域得以迅速发展。基于此, 本文对目前基于遥感数据的植物物种分类与识别中在分类对象复杂性、多源遥感数据整合、植物物候与纹理特征整合和分类算法技术等方面面临的挑战进行了总结, 并建议通过整合多时相监测数据、高光谱和激光雷达数据、短波红外等特定波谱信息、采用深度学习等方法来提高分类精度。 相似文献