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91.
Wen-Hsing Lin John T.-A. Hsu Shu-Yi Hsieh Chiung-Tong Chen Jen-Shin Song Shih-Chieh Yen Tsu Hsu Cheng-Tai Lu Chun-Hwa Chen Ling-Hui Chou Yung-Ning Yang Ching-Hui Chiu Ching-Ping Chen Ya-Ju Tseng Kuei-Jung Yen Ching-Fang Yeh Yu-Sheng Chao Teng-Kuang Yeh Weir-Torn Jiaang 《Bioorganic & medicinal chemistry》2013,21(11):2856-2867
Preclinical investigations and early clinical trials suggest that FLT3 inhibitors are a viable therapy for acute myeloid leukemia. However, early clinical data have been underwhelming due to incomplete inhibition of FLT3. We have developed 3-phenyl-1H-5-pyrazolylamine as an efficient template for kinase inhibitors. Structure–activity relationships led to the discovery of sulfonamide, carbamate and urea series of FLT3 inhibitors. Previous studies showed that the sulfonamide 4 and carbamate 5 series were potent and selective FLT3 inhibitors with good in vivo efficacy. Herein, we describe the urea series, which we found to be potent inhibitors of FLT3 and VEGFR2. Some inhibited growth of FLT3-mutated MOLM-13 cells more strongly than the FLT3 inhibitors sorafenib (2) and ABT-869 (3). In preliminary in vivo toxicity studies of the four most active compounds, 10f was found to be the least toxic. A further in vivo efficacy study demonstrated that 10f achieved complete tumor regression in a higher proportion of MOLM-13 xenograft mice than 4 and 5 (70% vs 10% and 40%). These results show that compound 10f possesses improved pharmacologic and selectivity profiles and could be more effective than previously disclosed FLT3 inhibitors in the treatment of acute myeloid leukemia. 相似文献
92.
Yihfen T. Yen Aarthi Karkal Mou Bhattacharya Rachel C. Fernandez 《Molecular membrane biology》2013,30(1):28-40
Yersinia pestis is a Gram-negative bacterium that causes plague. Currently, plague is considered a re-emerging infectious disease and Y. pestis a potential bioterrorism agent. Autotransporters (ATs) are virulence proteins translocated by a variety of pathogenic Gram-negative bacteria across the cell envelope to the cell surface or extracellular environment. In this study, we screened the genome of Yersinia pestis KIM for AT genes whose expression might be relevant for the pathogenicity of this plague-causing organism. By in silico analyses, we identified ten putative AT genes in the genomic sequence of Y. pestis KIM; two of these genes are located within known pathogenicity islands. The expression of all ten putative AT genes in Y. pestis KIM was confirmed by RT-PCR. Five genes, designated yapA, yapC, yapG, yapK and yapN, were subsequently cloned and expressed in Escherichia coli K12 for protein secretion studies. Two forms of the YapA protein (130 kDa and 115 kDa) were found secreted into the culture medium. Protease cleavage at the C terminus of YapA released the protein from the cell surface. Outer membrane localization of YapC (65 kDa), YapG (100 kDa), YapK (130 kDa), and YapN (60 kDa) was established by cell fractionation, and cell surface localization of YapC and YapN was demonstrated by protease accessibility experiments. In functional studies, YapN and YapK showed hemagglutination activity and YapC exhibited autoagglutination activity. Data reported here represent the first study on Y. pestis ATs. 相似文献
93.
Emilay B.T. Diogo Gleiston G. Dias Bernardo L. Rodrigues Tiago T. Guimarães Wagner O. Valença Celso A. Camara Ronaldo N. de Oliveira Mauro G. da Silva Vitor F. Ferreira Yen Galdino de Paiva Marilia O.F. Goulart Rubem F.S. Menna-Barreto Solange L. de Castro Eufrânio N. da Silva Júnior 《Bioorganic & medicinal chemistry》2013,21(21):6337-6348
In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17–24, 28–30 and 36–38 are described herein for the first time. Three of these novel compounds (28–30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 μM. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. 相似文献
94.
95.
Livestock wastewater that is discharged into rivers and ponds results in eutrophication, which would then cause an increase in microorganisms, microalgae, and macrophytes. The derivatives of which critically damage aquatic life and agricultural irrigation. This study designed a swine farm wastewater bioremediation system, by using tubular chained cyanobacteria-immobilized agar–alginate blocks and cyanobacteria biological absorption to reduce wastewater pollution. Swine farm wastewater was filtered through a long tube stuffed with cyanobacteria (Dermocarpella sp.)-immobilized agar–alginate blocks. The removal efficiencies of biological oxygen demand, chemical oxygen demand, phosphorous, ammonia, and suspension solids were evaluated. 相似文献
96.
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98.
Jiun Y. Yen Hadi Nazem-Bokaee Benjamin G. Freedman Ahmad I. M. Athamneh Dr. Ryan S. Senger 《Biotechnology journal》2013,8(5):581-594
Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H2 production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design “fine-tuned” metabolic engineering strategies in silico that can be implemented directly with available genomic tools. 相似文献
99.
Self‐Assembled BiFeO3‐ε‐Fe2O3 Vertical Heteroepitaxy for Visible Light Photoelectrochemistry 下载免费PDF全文
Le Thi Quynh Chien Nguyen Van Yugandhar Bitla Jhih‐Wei Chen Thi Hien Do Wen‐Yen Tzeng Sheng‐Chieh Liao Kai‐An Tsai Yi‐Chun Chen Chun‐Lin Wu Chih‐Huang Lai Chih‐Wei Luo Yung‐Jung Hsu Ying‐Hao Chu 《Liver Transplantation》2016,6(18)
Self‐assembled vertical heterostructure with a high interface‐to‐volume ratio offers tremendous opportunities to realize intriguing properties and advanced modulation of functionalities. Here, a heterostructure composed of two visible‐light photocatalysts, BiFeO3 (BFO) and ε‐Fe2O3 (ε‐FO), is designed to investigate its photoelectrochemical performance. The structural characterization of the BFO‐FO heterostructures confirms the phase separation with BFO nanopillars embedded in the ε‐FO matrix. The investigation of band structure of the heterojunction suggests the assistance of photoexcited carrier separation, leading to an enhanced photoelectrochemical performance. The insights into the charge separation are further revealed by means of ultrafast dynamics and electrochemical impedance spectroscopies. This work shows a delicate design of the self‐assembled vertical heteroepitaxy by taking advantage of the intimate contact between two phases that can lead to a tunable charge interaction, providing a new configuration for the optimization of photoelectrochemical cell. 相似文献
100.