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981.
Ling Xu Xiujuan Qu Xuejun Hu Zhitu Zhu Ce Li Enze Li Yanju Ma Na Song Yunpeng Liu 《FEBS letters》2013
Gastric cancer cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the resistance mechanism is not fully understood. In human gastric cancer MGC803 and BGC823 cells, TRAIL induces insulin-like growth factor-1 receptor (IGF-1R) pathway activation. Treatment with IGF-1R inhibitor OSI-906 or small interfering RNAs against IGF-1R, prevents IGF-1R pathway activation and increases TRAIL-induced apoptosis. The TRAIL-induced IGF-1R pathway activation is promoted by IGF-1R translocation into lipid rafts. Moreover, the translocation of IGF-1R into lipid rafts is regulated by Casitas B-lineage lymphoma b (Cbl-b). Taken together, TRAIL-induced IGF-1R activation antagonizes TRAIL-induced apoptosis by Cbl-b-regulated distribution of IGF-1R in lipid rafts. 相似文献
982.
The Burseraceae are a medium‐sized family in which 18 genera are currently recognised. They are the subject of a long‐term project to describe the pollen morphology from light, scanning electron and transmission electron microscopy. The pollen morphology of tribe Protieae has been published, as well as an account of the pollen of the African taxa in the family. Pollen data for the other two tribes, Bursereae and Canarieae, are more or less complete. The pollen of all the genera have been examined, with the exception of the recently described Pseudodacryodes Pierlot for which, currently, there is no pollen material available. This paper summarises the results. There is considerable variation in exine and aperture features between, and occasionally within, the genera and 14 major pollen types are defined, including two previously undescribed types: ‘Canarium oleiferum’ and ‘Canarium gracile’. The distribution of pollen characteristics throughout the family is compared with previously published tribal and subtribal groupings, as well as with current ideas of generic relationships from molecular analyses. Comparisons show notable congruence of pollen data with molecular data. To some extent pollen morphology is different for each of the subtribes. Nevertheless, there are some notable exceptions, for example, the pollen of Garuga and Boswellia are remarkably similar, although Garuga has been included, somewhat tenuously, in tribe Protieae, and Boswellia is included in tribe Bursereae, subtribe Boswelliinae. In a recent molecular tree Garuga and Boswellia appear to be closely related, and this supports the conclusion, based on several macromorphological characters as well as pollen, that Garuga should be transferred to tribe Bursereae. 相似文献
983.
Jiachuan Pan Fangchao Song Dacheng Ren 《Bioorganic & medicinal chemistry letters》2013,23(16):4648-4651
Pseudomonas aeruginosa is a major pathogen causing chronic pulmonary infections; for example, 80% of cystic fibrosis patients get infected by this bacterium as the disease progresses. Such chronic infections are challenging because P. aeruginosa exhibits high-level tolerance to antibiotics by forming biofilms (multicellular structures attached to surfaces), by entering dormancy and forming antibiotic tolerant persister cells, and by conversion to the mucoid phenotype. Recently, we reported that a synthetic quorum sensing inhibitor, (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8), can sensitize both planktonic and biofilm-associated persister cells of P. aeruginosa PAO1 to antibiotics at the concentrations non-inhibitory to its growth. In this study, we further characterized the effects of this compound on the mucoid strain P. aeruginosa PDO300. BF8 was found to reduce persistence during the growth of PDO300 and effectively kill the persister cells isolated from PDO300 cultures. In addition to planktonic cells, BF8 was also found to inhibit biofilm formation of PDO300 and reduce associated persistence. These findings broaden the activities of this class of compounds and indicate that BF8 also has other targets in P. aeruginosa in addition to quorum sensing. 相似文献
984.
Jung-eun Park Chiman Song Keehyun Choi Taebo Sim Bongjin Moon Eun Joo Roh 《Bioorganic & medicinal chemistry letters》2013,23(20):5515-5518
A series of 3,4-diarylpyrrolidin-2-one was designed, prepared and evaluated as triple reuptake inhibitors for antidepressant. Most compounds exhibited comparable in vitro efficacy as norepinephrine and dopamine transporter reuptake inhibitors. Especially, 2i showed better potency than GBR-12909 (IC50 = 14 nM) which was used as reference compound for dopamine transporter. In addition, 2a and 2b showed inhibition (5.17 μM–85.6 nM) for three transporters. 相似文献
985.
Rong Jiang Bozena Frackowiak Youseung Shin Xinyi Song Weimin Chen Li Lin Michael D. Cameron Derek R. Duckett Theodore M. Kamenecka 《Bioorganic & medicinal chemistry letters》2013,23(9):2683-2687
Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure. 相似文献
986.
Non hemolytic short peptidomimetics as a new class of potent and broad-spectrum antimicrobial agents
Ravichandran N. Murugan Binu Jacob Eun-Hee Kim Mija Ahn Hoik Sohn Ji-Hyung Seo Chaejoon Cheong Jae-Kyung Hyun Kyung S. Lee Song Yub Shin Jeong Kyu Bang 《Bioorganic & medicinal chemistry letters》2013,23(16):4633-4636
Since the bacterial resistance to antibiotics is increasing rapidly, numerous studies have contributed to the design and synthesis of potent synthetic mimics of antimicrobial peptides (AMPs). In an attempt to find the pharmacophore of short antimicrobial peptidomimetics through systematic tuning of hydrophobic and hydrophilic patterns, we have identified a set of short histidine-derived antimicrobial peptides (SAMPs) with potent and broad-spectrum activity. A combination of high antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), without hemolytic activity and proteolytic stability makes these molecules promising candidates for novel antimicrobial therapeutics. 相似文献
987.
Zhen-Wei Wu Hai-Wei Xu Gui-Fu Dai Meng-Jiao Liu Li-Ping Zhu Jian Wu Ya-Nan Wang Feng-Juan Wu Dan Zhao Ming-Fu Gao Shan-Shan Nie Wei Han Jing-Hui Song Hong-Min Liu 《Bioorganic & medicinal chemistry letters》2013,23(23):6421-6426
In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure–activity relationships were studied. Compared to 1, compounds 8a–8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs. 相似文献
988.
Guobin Cai Lisheng Deng Jian Xue Silvia N.J. Moreno Boris Striepen Yongcheng Song 《Bioorganic & medicinal chemistry letters》2013,23(7):2158-2161
The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, is an important human pathogen. 1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is essential to the organism and therefore a target for developing anti-toxoplasmosis drugs. In order to find potent inhibitors, we expressed and purified recombinant T. gondii DXR (TgDXR). Biochemical properties of this enzyme were characterized and an enzyme activity/inhibition assay was developed. A collection of 11 compounds with a broad structural diversity were tested against TgDXR and several potent inhibitors were identified with Ki values as low as 48 nM. Analysis of the results as well as those of Escherichia coli and Plasmodium falciparum DXR enzymes revealed a different structure–activity relationship profile for the inhibition of TgDXR. 相似文献
989.
Zhen Song Xiaoyan Zheng Binsheng Yang 《Protein science : a publication of the Protein Society》2013,22(11):1519-1530
CopC is a periplasmic copper Chaperone protein that has a β‐barrel fold and two metal‐binding sites distinct for Cu(II) and Cu(I). In the article, four mutants (Y79F, Y79W, Y79WW83L, Y79WW83F) were obtained by site‐directed mutagenesis. The far‐UV CD spectra of the proteins were similar, suggesting that mutations did not bring any significant changes in secondary structures. Meanwhile the effects of mutations on the protein's function were manifested by Cu(II) binding. Fluorescence lifetime measurement and quenching of tryptophan fluorescence by acrylamide and KI showed that the microenvironment around Trp83 was more hydrophobic than that around Tyr79 in apoCopC. Unfolding experiments induced by guanidinium chloride (GdnHCl), urea provided the conformational stability of each protein. The Δ<ΔG0element> obtained using the model of structural elements was used to show the role of Tyr79 and Trp83. On the one hand, the <ΔG0element> induced by urea for Y79F, Y79W have a loss of 6.51, 2.03 kJ/mol, respectively, compared with apoCopC, proving that replacement of Tyr79 by Phe or Trp all decreased the protein stability, meaning that the hydrogen bonds interactions between Tyr79 and Thr75 played an important role in stabilizing apoCopC. On the other hand, the <ΔG0element> induced by urea for Y79WW83L have a loss of 11.44 kJ/mol, but for Y79WW83F did a raise of 1.82 kJ/mol compared with Y79W. The replacement of Trp83 by Phe and Leu yields opposite effects on protein stability, which suggested that the aromatic ring of Trp83 was important in maintaining the hydrophobic core of apoCopC. 相似文献
990.