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901.
Xiao-Zhi Yang Xiao-Juan Diao Wen-Hui Yang Feng Li Guang-Wei He Guo-Qing Gong Yun-Gen Xu 《Bioorganic & medicinal chemistry letters》2013,23(7):2089-2092
A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50 = 3.7 ± 1.0 μmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50 = 7.8 ± 1.5 μmol/kg). 相似文献
902.
Hui-Yu Yi Xiao-Juan Deng Wan-Ying Yang Cong-Zhao Zhou Yang Cao Xiao-Qiang Yu 《Insect biochemistry and molecular biology》2013,43(7):612-625
Gloverins are basic, glycine-rich and heat-stable antibacterial proteins (~14- kDa) in lepidopteran insects with activity against Escherichia coli, Gram-positive bacteria, fungi and a virus. Hyalophora gloveri gloverin adopts a random coil structure in aqueous solution but has α-helical structure in membrane-like environment, and it may interact with the lipid A moiety of lipopolysaccharide (LPS). Manduca sexta gloverin binds to the O-specific antigen and outer core carbohydrate of LPS. In the silkworm Bombyx mori, there are four gloverins with slightly acidic to neutral isoelectric points. In this study, we investigate structural and binding properties and activities of B. mori gloverins (BmGlvs), as well as correlations between structure, binding property and activity. Recombinant BmGlv1-4 were expressed in bacteria and purified. Circular dichroism (CD) spectra showed that all four BmGlvs mainly adopted random coli structure (>50%) in aqueous solution in regardless of pH, but contained α-helical structure in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), smooth and rough mutants (Ra, Rc and Re) of LPS and lipid A. Plate ELISA assay showed that BmGlvs at pH 5.0 bound to rough mutants of LPS and lipid A but not to smooth LPS. Antibacterial activity assay showed that positively charged BmGlvs (at pH 5.0) were active against E. coli mutant strains containing rough LPS but inactive against E. coli with smooth LPS. Our results suggest that binding to rough LPS is the prerequisite for the activity of BmGlvs against E. coli. 相似文献
903.
Hualong Fu Lihai Yu Mengchao Cui Jinming Zhang Xiaojun Zhang Zijing Li Xuedan Wang Jianhua Jia Yanping Yang Pingrong Yu Hongmei Jia Boli Liu 《Bioorganic & medicinal chemistry》2013,21(13):3708-3714
A novel series of fluorinated 2-phenylindole derivatives were synthesized and evaluated as β-amyloid imaging probes for PET. The in vitro inhibition assay demonstrated that their binding affinities for Aβ1–42 aggregates ranged from 28.4 to 1097.8 nM. One ligand was labeled with 18F ([18F]1a) for its high affinity (Ki = 28.4 nM), which was also confirmed by in vitro autoradiography experiments on brain sections of transgenic mouse (C57BL6, APPswe/PSEN1, 11 months old, male). In vivo biodistribution experiments in normal mice showed that this radiotracer displayed high initial uptake (5.82 ± 0.51% ID/g at 2 min) into and moderate washout (2.77 ± 0.31% ID/g at 60 min) from the brain. [18F]1a could be developed as a promising new PET imaging probe for Aβ plaques although necessary modifications are still needed. 相似文献
904.
Ya-Li Song Yun-Fang Dong Tao Yang Chao-Chao Zhang Li-Min Su Xin Huang Dong-Nuan Zhang Geng-Liang Yang Yu-Xin Liu 《Bioorganic & medicinal chemistry》2013,21(24):7624-7627
In an effort to develop potent anti-cancer chemopreventive agents that act on topoisomerase II, a novel series of bisindolylalkanes analogues such as 3,3′-(thiochroman-4,4-diyl)bis(1H-indole) are synthesized. Structures of all compounds are elucidated by 1H NMR, 13C NMR and HRMS. Anti-proliferative activities for all of these compounds are investigated by the method of MTT assay on 7 human cancer lines. Most of them showed antitumor activities in vitro, the half maximal inhibitory concentration (IC50) value is 7.798 μg/mL of 3a against MCF7. Compound 3a showed comparable topoisomerase II inhibitory activity to etoposide (VP-16) at 100 μM concentration. The rest of the compounds also showed varying degree topoisomerase II inhibitory activity. 相似文献
905.
Xiaoke Guo Qian Yang Jing Xu Li Zhang Hongxi Chu Peng Yu Yingying Zhu Jinglian Wei Weilin Chen Yaozhong Zhang Xiaojin Zhang Haopeng Sun Yiqun Tang Qidong You 《Bioorganic & medicinal chemistry》2013,21(21):6466-6476
Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel is reported as an efficacious and safe target for the treatment of AF. In this paper, we designed and synthesized three series of compounds through modifying the lead compound RH01617 that was screened out by the pharmacophore model we reported earlier. All of the compounds were evaluated by the whole-patch lamp technology and most of them possessed potent inhibitory activities against Kv1.5. Compounds IIIi and IIIl were evaluated for the target selectivity as well as the pharmacodynamic effects in an isolated rat model. Due to the promising pharmacological behavior, compound IIIl deserves further pharmacodynamic and pharmacokinetic evaluations. 相似文献
906.
Fei Yu Li Mei Li Pei Pei Yang Xiu Qin Wang 《Journal of plant biochemistry and biotechnology.》2013,22(3):324-334
Two full-length hexokinase (HXK, EC 2.7.1.1) cDNAs, VvHXK1 with 1,413 bp and VvHXK2 with 1,458 bp were cloned from grape berries (Vitis vinifera L. Cabernet Sauvignon). VvHXK1 and VvHXK2 genes sequence from grape berries were deposited in GenBank under the accession number JN118544 and JN118545, respectively. The homology of the amino acid of VvHXK1 or VvHXK2 was very similar to ‘Pinot Noir’ grape HXK sequence, their similarties were 99.36 % and 98.97 %, respectively. More intuitive phylogenetic tree showed that the homology of amino acid sequence VvHXK1 with melon CmHXK1 was 86 %, and VvHXK2 homology with rice OsHXK3 was 83 %. The HXK proteins were successfully expressed in plasmid pET-30a (+) vectors in Escherichia coli BL21 (DE3) pLysS. The expressed proteins were purified using Ni-NTA agarose column and used to produce HXK1 antibody and conducted HXK protein blotting analysis. The results,suggested that one polypeptide band of about 51 kDa HXK protein can be detected in grape berries, HXK protein level was the highest during early grape berry development, but the lowest from 50d to 60d during development. Biochemical analysis of two hexokinase isozymes indicated that glucose was the optimal substrate of HXK, The isoelectric points of the two isozymes were 5.8 and 5.6, respectively. And the optimum pH was about 8.0. These results provide a substantial basis for the further studies of functions of grape HXKs to manipulate sugar content of grape berries. 相似文献
907.
Objectives To explore whether the angiotensin T -converting enzyme (ACE) I/D (insertion/ deletion) polymorphism is associated with the susceptibility to high altitude pulmonary edema (HAPE) in the Han Chinese. Methods One hundred and forty-seven HAPE-p (HAPE patients) and 193 HAPE-r (HAPE resistants) were enrolled from the Yushu earthquake reconstruction workers in Qinghai province where the altitude is over 3 500 m above sea level. Blood samples were collected from each of the HAPE-p and HAPE-r groups. Information about physiological phenotypes was obtained via fieldwork investigation. The ACE-I/D polymorphism in HAPE-p and HAPE-r was detected by polymerase chain reaction (PCR). Results The SaO2 was significantly lower while HR was significantly higher in HAPE-p group than those in HAPE-r group. The genotype frequencies of ACE-I/D for II, ID, DD in HAPE-r and HAPE-p groups were 0.430, 0.446, 0.124 and 0.435, 0.469, 0.095, respectively, the allelic frequencies of I and D were 0.650, 0.350 and 0.670, 0.330, respectively. The OR of ID, DD and D alleles relative to II for HAPE was 0.961 (0.610-1.514), 1.322 (0.634-2.758) and 1.080 (0.783-1.489). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between HAPE-p and HAPE-r groups. Conclusions There is no relation between ACE-I/D polymorphism and HAPE in the Han Chinese. 相似文献
908.
909.
Ying Zhao Xue Li Mu-Yan Cai Ke Ma Jing Yang Jingyi Zhou Wan Fu Fu-Zheng Wei Lina Wang Dan Xie Wei-Guo Zhu 《Cell research》2013,23(4):491-507
Autophagy is activated to maintain cellular energy homeostasis in response to nutrient starvation. However, autophagy is not persistently activated, which is poorly understood at a mechanistic level. Here, we report that turnover of FoxO1 is involved in the dynamic autophagic process caused by glutamine starvation. X-box-binding protein-1u (XBP-1u) has a critical role in FoxO1 degradation by recruiting FoxO1 to the 20S proteasome. In addition, the phosphorylation of XBP-1u by extracellular regulated protein kinases1/2 (ERK1/2) on Ser61 and Ser176 was found to be critical for the increased interaction between XBP-1u and FoxO1 upon glutamine starvation. Furthermore, knockdown of XBP-1u caused the sustained level of FoxO1 and the persistent activation of autophagy, leading to a significant decrease in cell viability. Finally, the inverse correlation between XBP-1u and FoxO1 expression agrees well with the expression profiles observed in many human cancer tissues. Thus, our findings link the dynamic process of autophagy to XBP-1u-induced FoxO1 degradation. 相似文献
910.