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931.
Guo-Liang Chen Li-Hui Wang Jian Wang Kang Chen Man Zhao Zhao-Zhu Sun Shuang Wang Hong-Li Zheng Jing-Yu Yang Chun-Fu Wu 《Bioorganic & medicinal chemistry letters》2013,23(13):3891-3895
Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-targeting agent is derived from bexarotene and suberoylanilide hydroxamic acid (SAHA), prototypical RXR agonist and HDAC inhibitor, respectively. Molecular docking studies demonstrate that this agent has a relatively strong affinity to RXR and HADC. Importantly, it presents the potentials of activation of RXR and inhibition of HDAC in both cell-free and whole-cell assays, and displays anti-proliferative effect on representative cancer cell lines and drug-resistant cancer cell lines. 相似文献
932.
Xianwen Cao Jing Jiang Shoude Zhang Lili Zhu Juan Zou Yanyan Diao Weilie Xiao Lei Shan Handong Sun Weidong Zhang Jin Huang Honglin Li 《Bioorganic & medicinal chemistry letters》2013,23(11):3329-3333
Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation. 相似文献
933.
Dong Xiao Anandan Palani Xianhai Huang Michael Sofolarides Wei Zhou Xiao Chen Robert Aslanian Zhuyan Guo James Fossetta Fang Tian Prashant Trivedi Peter Spacciapoli Charles E. Whitehurst Daniel Lundell 《Bioorganic & medicinal chemistry letters》2013,23(11):3262-3266
Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay. 相似文献
934.
Li‐Yuan Wang Lin Zeng Yan‐Sheng Shi Zheng‐Liang Qiu Hua‐Hu Ye Xiao‐Fei Zhang Qing‐Bin Lu Michael Kosoy Wei Liu Wu‐Chun Cao 《Molecular ecology》2013,22(8):2118-2127
Bartonella quintana is a bacterium that causes a broad spectrum of diseases in humans including trench fever. Humans were previously considered to be the primary, if not the only, reservoir hosts for B. quintana. To identify the animal reservoir and extend our understanding of the ecological and evolutionary history of B. quintana, we examined blood samples from macaques and performed multilocus sequence typing (MLST) analysis. We demonstrated the prevalence of B. quintana infection was common in macaques from main primate centres in mainland China. Overall, 18.0% (59/328) of rhesus macaques and 12.7% (39/308) of cynomolgus macaques were found to be infected with B. quintana by blood culture and/or polymerase chain reaction. The infection was more frequently identified in juvenile and young monkeys compared with adult animals. In contrast with the relatively low level of sequence divergence of B. quintana reported in humans, our investigation revealed much higher genetic diversity in nonhuman primates. We identified 44 new nucleotide variable sites and 14 novel sequence types (STs) among the B. quintana isolates by MLST analysis. Some STs were found only in cynomolgus macaques, while some others were detected only in rhesus macaques, suggesting evidence of host‐cospeciation, which were further confirmed by phylogenetic analysis and Splits decomposition analysis. Our findings suggest that trench fever may primarily be a zoonotic disease with macaques as the natural hosts. 相似文献
935.
Stripe rust is a devastating fungal disease of wheat worldwide which is primarily caused by Puccinia striiformis f. sp tritici. Transgenic wheat (Triticum aestivum L.) expressing rice class chitinase gene RC24 were developed by particle bombardment of immature embryos and tested for resistance to Puccinia striiformis f.sp tritici. under greenhouse and field conditions. Putative transformants were selected on kanamycin-containing media. Polymease chain reaction indicated that RC24 was transferred into 17 transformants obtained from bombardment of 1,684 immature embryos. Integration of RC24 was confirmed by Southern blot with a RC24-labeled probe and expression of RC24 was verified by RT-PCR. Nine transgenic T1 lines exhibited enhanced resistance to stripe rust infection with lines XN8 and BF4 showing the highest level of resistance. Southern blot hybridization confirmed the stable inheritance of RC24 in transgenic T1 plants. Resistance to stripe rust in transgenic T2 and T3 XN8 and BF4 plants was confirmed over two consecutive years in the field. Increased yield (27–36 %) was recorded for transgenic T2 and T3 XN8 and BF4 plants compared to controls. These results suggest that rice class I chitinase RC24 can be used to engineer stripe rust resistance in wheat. 相似文献
936.
Li Zhu Tsuneyuki Tatsuke Hiroaki Mon Zhiqing Li Jian Xu Jae Man Lee Takahiro Kusakabe 《Insect biochemistry and molecular biology》2013,43(8):664-674
The Tudor-sn protein, which contains four staphylococcal nuclease domains and a Tudor domain, is a ubiquitous protein found in almost all organisms. It has been reported that Tudor-sn in mammals participates in various cellular pathways involved in gene regulation, cell growth, and development. In insects, we have previously identified a Tudor-sn ortholog in the silkworm, Bombyx mori, and detected its interactions between with Argonaute proteins. The role of Tudor-sn in silkworm, however, still remains largely unknown. In this study, we demonstrated that silkworm Tudor-sn is a stress granule (SG) protein, and determined its interactions with other SG proteins using Bimolecular Fluorescence Complementation assay and Insect Two-Hybrid method. Depletions of Argonaute proteins and SG-marker protein Tia1 by RNAi impaired the involvement of Tudor-sn in the SG formation. Protein domain deletion analysis of Tudor-sn demonstrated that SN2 is the key domain required for the aggregation of Tudor-sn in SGs. 相似文献
937.
Qian-Ru Du Dong-Dong Li Ya-Zhou Pi Jing-Ran Li Jian Sun Fei Fang Wei-Qing Zhong Hai-Bin Gong Hai-Liang Zhu 《Bioorganic & medicinal chemistry》2013,21(8):2286-2297
A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9–44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56–3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study. 相似文献
938.
939.
为研制抗血吸虫疫苗提供实验依据,探讨了抗血吸虫SjGST-32核酸疫苗与蛋白疫苗联合免疫的免疫增强效应及免疫应答特征。将日本血吸虫DNA疫苗VR1012-SjGST-32与重组蛋白疫苗rSjGST-32分别在第0、2和4周免疫小鼠,在第6周攻击感染日本血吸虫尾蚴,攻击感染45 d后剖杀小鼠,计算减虫率、检卵率以及检测肝脏病理变化,观察免疫保护效果;检测小鼠血清中特异性IgG抗体滴度,T细胞增殖反应和抗原特异性CD4+IFN-γ+、CD4+IL-4+和CD4+IL-10+的数量,探讨免疫应答特征。结果显示,DNA初免-蛋白加强的联合免疫组的保护作用优于单独免疫组,显著提高了减虫率(42.3%)和减卵率(59.6%),并且能够显著减轻血吸虫虫卵对肝脏的病理损害;进一步发现,DNA疫苗和蛋白疫苗联合应用增强了机体T淋巴细胞增殖反应、抗体IgG滴度以及抗原特异性CD4+IFN-γ+的产生。这些研究为新型血吸虫疫苗的优化设计和合理应用提供了依据。 相似文献
940.
以授粉后具花闭合特性的紫茉莉为研究材料,通过在不同天气状况下作去花冠和存留花冠处理,观察花冠对花粉活力、柱头可授性及结实率等繁殖特性的影响。结果表明:紫茉莉自然存留花冠比去花冠的花粉活力、柱头可授性、柱头上的花粉数及柱头上花粉萌发率各指标达最高值的时间重叠性更强,并以阴天存留花冠的最强。存留花冠通过这种时间的重叠性来保证花粉在柱头上的萌发,产生了有利的繁殖适合度。越晚去花冠结实率越高,结实率呈现花闭合自然存留花冠>花冠闭合期去花冠>散粉初期去花冠>花冠展开期去花冠的规律。因此,花冠对紫茉莉繁殖适合度具有利影响。紫茉莉花冠的存留提高了繁殖适合度,增强了对环境的适应能力。 相似文献