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Integrative System Biology Strategies for Disease Biomarker Discovery
Haiyuan Zhang, Hao Hu, Cao Deng, Yeona Chun, Shengtao Zhou, Fuqiang Huang and Qin Zhou
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00036]
The application of High-throughput siRNA Screening Technology to study Host-Pathogen Interactions
Li Ou, Dan Duan, Jinhua Wu, Edouard Nice and Canhua Huang
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00037]
Recent Advances in Screening of Natural Products For Antimicrobial Agents
Meng Zhou, Hao Luo, Zhi Li, Feng Wu, Canhua Huang, Zhenyu Ding and Rui Li
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00038]
Chemistry-based functional proteomics to identify novel deubiquitylating enzymes involved in viral infection
Yunlong Lei, Ke Xie, Kai Huang, Hong Wu and Canhua Huang
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00039]
Computer-aided drug design: lead discovery and optimization
Mingli Xiang, Yu Cao, Wenjie Fan, Lijuan Chen and Yirong Mo
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00040]
A new way of probing reaction networks: analyzing multidimensional parameter space
Raoul Naumann d’Alnoncourt, Yury V. Kolen’ko, Robert Schlögl and Annette Trunschke
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00041]
Recent Trends in Chiral Separations on Immobilized Polysaccharides
CSPs
Zeid A. AL-Othman, Imran Ali, Mohd. Asim and Tabrez A. Khan
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00042]
Microwave-assisted Multiconponent Reactions: Rapid and Regioselective Formation of New Extended Angular Fused Aza-heterocycles
Shu-Liang Wang, Ge Zhang, Ding Jie, Bo Jiang, Xing-Han Wang and Shu-Jiang Tu
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00043]
Light Fluorous-tagged Traceless One-pot Synthesis of Benzimidazoles Facilitated by Microwave Irradiation
Chih-Chung Tseng, Cheng-Hsun Tasi and Chung-Ming Sun
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00044]
Novel Isocyanide-Based Three-Component Synthesis of Substituted 9H-furo[2,3-f]chromene-8,9-dicarboxylates in water
Faramarz Rostami Charati, Zinatossadat Hossaini and Mohammad A. Khalilzadeh
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00045]
Microwave-assisted synthesis of cyclopentanones using the relevant phosphorus ylides
Faramarz Rostami Charati, Zinatossadat Hossaini, Majid Moradian, Ali Jafari and Abodolreza Yazdani
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00046]
QSAR Modeling and Design of Cationic Antimicrobial Peptides Based on Structural Properties of Amino Acids
Yuanqiang Wang, Yuan Ding, Haixia Wen, Yong Lin, Yong Hu,Ya Zhang, Qingyou Xia and Zhihua Lin
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00047]
Classification of Acetylcholinesterase Inhibitors and Decoys by a Support Vector Machine
Kai Wang, Xiaoying Hu, Zhi Wang and Aixia Yan
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00048]
Insight into the structural requirements of narlaprevir-type inhibitors of NS3/NS4A protease based on HQSAR and molecular field analyses
Jingyu Zhu, Youyong Li, Huidong Yu, Liling Zhang, Xinliang Mao and Tingjun Hou
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00049]
SPED-(Styrene-Polyethyleneglycol Diacrylate-9-Decen-1-ol)- A Novel Resin for Solid Phase Peptide Synthesis; Synthesis and Characterization of Biologically Potent Endothelin Classes of Peptides
M.A. Siyad and G.S. Vinod Kumar
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00050]
Determination of 7,12-Dimethylbenz[a]anthracene in Orally Treated Rats by High-performance Liquid Chromatography and Transfer Stripping Voltammetry
Yavuz Yardım, Abdulkadir Levent, Suat Ekin, Ertuğrul Keskin, Gökhan Oto and Zühre Şentürk
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00051]
A simple and effective approach to the synthesis of isoquinoline derivatives under Solvent-free conditions
Zinatossadat Hossaini, Faramarz Rostami-Charati, Somayeh Firoziyan, Maryam Sabbaghan and Mohammad A. Khalilzadeh
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00052]
Parallel Microwave-assisted Synthesis of Ionic Liquids and Screening for Denitrogenation of Straight-Run Diesel Feed by liquid-liquid extraction
Miguel A. Cerón, Diego J. Guzmán-Lucero, Jorge F. Palomeque and Rafael Martínez-Palou
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00053]
A clean procedure for synthesis of pyrido[d]pyrimidine derivatives under solvent-free conditions catalyzed by ZrO2 nanoparticles
Shahrzad Abdolmohammadi and Saeed Balalaie
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00054]
Iodocyclization, Followed by Palladium-Catalyzed Coupling: A Versatile Strategy for Heterocyclic Library Construction
Anton V. Dubrovskiy, Nataliya A. Markina and Richard C. Larock
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00055]
Development and validation of a fluorescence-based HTS assay for the identification of P/Q-type calcium channel blockers
Mario Mezler, David Hermann, Andrew M. Swensen, Andreas Draguhn, Georg C. Terstappen, Gerhard Gross, Hans Schoemaker, Gail Freiberg, Steve Pratt, Sujatha M. Gopalakrishnan and Volker Nimmrich
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00056]
A High Throughput Scintillation Proximity Imaging Assay for Protein Methyltransferases
Glorymar Ibáñez, David Shum, Gil Blum, Bhavneet Bhinder, Constantin Radu, Christophe Antczak, Minkui Luo and Hakim Djaballah
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00057]
Discovery and Preliminary SAR of 5-Arylidene-2,2-dimethyl-
1,3-dioxane-4,6-diones as Platelet Aggregation Inhibitors
Abdelaziz El Maatougui, Jhonny Azuaje, Alberto Coelho, Ernesto Cano, Matilde Yañez, Mari Carmen López, Vicente Yaziji, Carlos Carbajales and Eddy Sotelo
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00058]
A support vector machine based method to predict success for polymerase chain reactions
Xiaoqing Yu, Xiaoqi Zheng, Liangyu Meng, Chun Li and Jun Wang
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00059]
PEG-mediated catalyst-free expeditious synthesis of polysubstituted anilines and benzenes via the reaction of malononitrile and β-ketoester derivatives in the presence of activated acetylenes
Mohammad Piltan, Loghman Moradi, Hiwa Salimi, Kiomars Zargoosh and Seyed Amir Zarei
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00060]
Ganoderma Lucidum Polysaccharides Exert Anti-hyperglycemic Effect on Streptozotocin-induced Diabetic Rats through Affecting β-cells
Jusheng Zheng, Bin Yang, Yinghua Yu, Qi Chen and Tao Huang, Duo L
[Abstract] [FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00061]
Abstracts
Integrative System Biology Strategies for Disease Biomarker Discovery
Haiyuan Zhang, Hao Hu, Cao Deng, Yeona Chun, Shengtao Zhou, Fuqiang Huang and Qin Zhou
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00036]
Biomarkers are currently widely used to diagnose diseases, monitor treatments, and evaluate potential drug candidates. Research of differential Omics accelerate the advancements of biomarkers’ discovery. By extracting biological knowledge from the ‘omics’ through integration, integrative system biology creates predictive models of cells, organs, biochemical processes and complete organisms, in addition to identifying human disease biomarkers. Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. Several integrative system biology approaches have been developed and applied to the discovery of disease biomarkers from databases. In this review, we highlight several of these approaches and identify future steps in the context of the field of integrative system biology.
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The application of High-throughput siRNA Screening Technology to study Host-Pathogen Interactions
Li Ou, Dan Duan, Jinhua Wu, Edouard Nice and Canhua Huang
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00037]
Recent advances in high-throughput screening technologies have accelerated the identification and characterization of potential factors involved in host-virus interactions, facilitating early detection and diagnosis of diseases, as well as providing promising drug targets. The last decade has seen a plethora of successful examples of high-throughput screening approaches, especially siRNA screening. With support from protein interaction studies, mRNA expression profiling, and bioinformatics, siRNA screening has also been successfully utilized to identify host factors required for a number of viruses including HIV, West Nile virus and H1N1 virus. Such studies have raised the awareness of virologists, and have opened a new chapter of global analysis of host-pathogen interactions. However, to play a more defining role in prognostics, diagnostics and therapeutics for virus diseases, acknowledged drawbacks, including false positives and negatives, inherent in this technology, must be successfully addressed.
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Recent Advances in Screening of Natural Products For Antimicrobial Agents
Meng Zhou, Hao Luo, Zhi Li, Feng Wu, Canhua Huang, Zhenyu Ding and Rui Li
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00038]
It has been a very long history for human to resist diseases. During this period, a large number of drugs that could kill or inhibit the growth of microbe has been discovered, most of which were natural products. However, there may still be a large amount of antimicrobial medicines in natural compounds which have not been found yet. The ways of screening for antimicrobial always cost a long time and need a lot of manpower before. However, in recent years, a lot of new antimicrobial targets, antimicrobial drugs and screening methods which are simpler, faster and more efficient have been invented. In this paper the newly discovered targets, natural products and representative technologies were reviewed, which were expected to make some contributions to the research and development of medicines.
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Chemistry-based functional proteomics to identify novel deubiquitylating enzymes involved in viral infection
Yunlong Lei, Ke Xie, Kai Huang, Hong Wu and Canhua Huang
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00039]
Ubiquitylation is a reversible post-translational modification pathway that regulates a variety of cellular processes including protein degradation and trafficking, intracellular localization, DNA repair, immune response and cell-cycle progression. Deubiquitylating enzymes (DUBs) can remove the ubiquitin from the modified proteins and reverse the ubiquitylation-induced biological processes; hence it isn’t hard to understand that viral pathogens take advantage of the host cell ubiquitin system through disturbing DUBs, for infection and replication. Although accumulated virus-related DUBs have been defined, but how viruses regulate their expression and activities is poor understand because of limitation of technologies. Recently, chemistry-based functional proteomics, which can not only monitor the alteration of abundance but also changes in activity of enzymes, was used to study the function of DUBs involved in virus infection and held much promise. Theses works suggest that chemistry-based functional proteomics is a potent strategy for high throughput screening of virus-related DUBs and exploring their roles in virus infection.
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Computer-aided drug design: lead discovery and optimization
Mingli Xiang, Yu Cao, Wenjie Fan, Lijuan Chen and Yirong Mo
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00040]
Over the past decade, there have been remarkable advances in the area of computer-aided drug design (CADD), which has been applied at almost all stages in the drug discovery pipeline. The generation of initial lead compounds and the subsequent optimization aimed at improving potency and pharmacological properties are the core activities among all. The development in these aspects over the past years will be the focus of this review.
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A new way of probing reaction networks: analyzing multidimensional parameter space
Raoul Naumann d’Alnoncourt, Yury V. Kolen’ko, Robert Schlögl and Annette Trunschke
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00041]
Technically relevant partial oxidation reactions represent complex reaction networks. Establishing a kinetic model for a system of multiple consecutive and parallel reaction steps is a challenging goal. The synthesis of acrylic acid by oxidation of propane using MoVTeNb mixed oxide as catalyst is such a reaction network. In an on-going study, a 10-fold parallel reactor set-up is used to vary systematically reaction conditions in a broad range over a single, well-defined MoVTeNb oxide. Selectivity and product yield in a multidimensional parameter space can give insight into the reaction network. Apparent activation energies and reaction orders of propane are derived for several conditions. Optimum reaction conditions within the investigated parameter space are specified. The results presented within this contribution contain about 200 data points measured in steady states each corresponding to reaction conditions that differ in temperature, contact time, and propane feed concentration. The fact that this data was collected in less than two months shows clearly the advantage of parallel screening of reaction conditions for mechanistic studies.
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Recent Trends in Chiral Separations on Immobilized Polysaccharides
CSPs
Zeid A. AL-Othman, Imran Ali, Mohd. Asim and Tabrez A. Khan
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00042]
Polysaccharide CSPs are recognized widely in chiral chromatography but the introduction of immobilized phases (Chiralpak IA, Chiralpak IB and Chiralpak IC columns) is a remarkable achievement. The immobilized CSPs can be used with organic, normal and reversed phase modes; even with prohibited solvents too (tetrahydrofuran, chlorofom, dichloromethane, acetone, 1,4-dioxane, ethylacetate, and certain other ethers). Their susceptibilities to work with a wide range of solvents have increased the range of applications including chiral recognition mechanisms. Besides, these are also useful for monitoring the progress of stereo-specific reactions; normally need prohibited solvents. The present review describes the various aspects of commercial available immobilized chiral columns. Attempts have been made to discuss immobilized polysaccharides CSPs, immobilized vs coated CSPs, comparison of immobilized CSPs, method development, optimization, chiral recognition mechanism and applications. The chiral recognition capabilities of commercial columns were in the order of Chiralpak IA > Chiralpak IB > Chiralpak IC columns; but complimentary to each other. Of course, these CSPs are not fully developed and need more advancements and applications. Definitely, the future of immobilized CSPs is quite better. Hopefully, in the coming years they will be the choice of the chromatographers for chiral separations in liquid chromatography.
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Microwave-assisted Multiconponent Reactions: Rapid and Regioselective Formation of New Extended Angular Fused Aza-heterocycles
Shu-Liang Wang, Ge Zhang, Ding Jie, Bo Jiang, Xing-Han Wang and Shu-Jiang Tu
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00043]
A new multicomponent domino reaction for rapid and regioselective synthesis of highly functionalized benzo[h]naphtho[2,3-a]acridine-15,16(5H,14H)-diones has been established. The reaction can be conducted by using readily available and inexpensive substrates under microwave irradiation. The procedures are facile, avoiding time-consuming and costly syntheses, tedious work-up and purifications of precursors as well as protection/deprotection of functional groups. This method is much more efficient due to short reaction times and easy work up. The resulting naphthoacridines have been readily converted into benzoquinoxaline-fused benzoquinoline analogues by treating with benzene-1,2-diamine under microwave irradiation. The structural assignment has been ambiguously confirmed by X-ray analysis. A new mechanism has been proposed for this new multicomponent domino process.
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Light Fluorous-tagged Traceless One-pot Synthesis of Benzimidazoles Facilitated by Microwave Irradiation
Chih-Chung Tseng, Cheng-Hsun Tasi and Chung-Ming Sun
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00044]
A novel protocol for rapid assemble of benzimidazole framework has been demonstrated. This method incorporated with light fluorous-tag provides a convenient method for diversification of benzimidazoles and for easy purification via fluorous solid-phase extraction (F-SPE) in a parallel manner. The key transformation of this study involves in situ reduction of aromatic nitro compound, amide formation, cyclization and aromatization promoted by microwave irradiation in a one-pot fashion. The strategy is envisaged to be applied for establishment of drug-like small molecule libraries for high throughput screening.
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Novel Isocyanide-Based Three-Component Synthesis of Substituted 9H-furo[2,3-f]chromene-8,9-dicarboxylates in water
Faramarz Rostami Charati, Zinatossadat Hossaini and Mohammad A. Khalilzadeh
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00045]
Three-component reaction of 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone, dialkyl acetylenedicarboxylates and isocyanides in water are described as efficient and green synthetic procedure for preparation of 9H-furo[2,3-f]chromene-8,9-dicarboxylates in excellent yield. In these reactions, 1-(6-hydroxy-2-isopropenyl-1-benzofuran-yl)-1-ethanone was extracted from rhizomes of Petasites hybridus from northern Iran. The structure of this compound was determined by 1H, 13C-NMR and IR spectroscopy and confirmed by X-ray diffraction analysis. This procedure provides rapid access to novel and diversely substituted 9H-furo[2,3-f]chromene-8,9-dicarboxylate derivatives.
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Microwave-assisted synthesis of cyclopentanones using the relevant phosphorus ylides
Faramarz Rostami Charati, Zinatossadat Hossaini, Majid Moradian, Ali Jafari and Abodolreza Yazdani
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00046]
A one-pot synthesis of cyclopentanone derivatives from phosphorus ylide under lab-type microwave assisted methodology was described. The phosphorus ylides were obtained via the reaction of activated acetylenic compounds, ethyl 4-chloroacetoacetate and triphenylphosphine. The structure of phosphorus ylides was assigned by 1H, 13C and 31P-NMR. The phosphorus ylides as precursor were crystallized as two enantiomers (R,R) and (S,S) and the structure of was confirmed by single X-ray crystallography.
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QSAR Modeling and Design of Cationic Antimicrobial Peptides Based on Structural Properties of Amino Acids
Yuanqiang Wang, Yuan Ding, Haixia Wen, Yong Lin, Yong Hu,Ya Zhang, Qingyou Xia and Zhihua Lin
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00047]
Drug resistance to existing antibiotics poses alarming threats to global public health, which inspires heightened interests in searching for new antibiotics, including antimicrobial peptides (AMPs). Accurate prediction of antibacterial activities of AMPs may expedite novel AMP design and reduce the costs and efforts involved in laboratory screening. In the present study, a novel quantitative prediction method of AMP was established by quantitative structure-activity relationship (QSAR) modeling based on the physicochemical properties of amino acids. The indices of these physicochemical properties were used to define AMP. The structural variables were optimized by stepwise regression (STR). Three series of AMPs from the QSAR model were constructed by multiple linear regressions (MLR). These QSAR models showed good performance in reliability and predictability. The normalized regression coefficients of the QSAR model and the contribution of amino acids at each position of AMP may determine the suitableness of a particular residue at any given position. QSAR models constructed by STR-MLR should prove to be useful tools in peptide design with respect to the calculation, explanation, good and reliable performance, and definition of physiochemical properties.
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Classification of Acetylcholinesterase Inhibitors and Decoys by a Support Vector Machine
Kai Wang, Xiaoying Hu, Zhi Wang and Aixia Yan
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00048]
Acetylcholinesterase has long been considered as a target for Alzheimer disease therapy. In this work, several classification models were built for the purpose of distinguishing acetylcholinesterase inhibitors (AChEIs) and decoys. Each molecule was initially represented by 211 ADRIANA.Code and 334 MOE descriptors. Correlation analysis, F-score and attribute selection methods in Weka were used to find the best reduced set of descriptors, respectively. Additionally, models were built using a Support Vector Machine and evaluated by 5-, 10-fold and leave-one-out cross-validation. The best model gave a Matthews Correlation Coefficient (MCC) of 0.99 and a prediction accuracy (Q) of 99.66% for the test set. The best model also gave good result on an external test set of 86 compounds (Q=96.51%, MCC=0.93). The descriptors selected by our models suggest that H-bond and hydrophobicity interactions are important for the classification of AChEIs and decoys.
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Insight into the structural requirements of narlaprevir-type inhibitors of NS3/NS4A protease based on HQSAR and molecular field analyses
Jingyu Zhu, Youyong Li, Huidong Yu, Liling Zhang, Xinliang Mao and Tingjun Hou
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00049]
In the life cycle of hepatitis C virus (HCV), NS3/NS4A protease has been proved to play a vital role in the replication of the HCV virus. Narlaprevir and its derivatives, the inhibitors of NS3/NS4A, would be potentially developed as important anti-HCV drugs in the future. In this study, quantitative structure-activity relationship (QSAR) analyses for 190 narlaprevir derivatives were conducted using comparative molecular field analysis (CoMFA), comparative molecular indices analysis (CoMSIA) and hologram quantitative structure–activity relationship (HQSAR) techniques. Both of the best CoMFA and HQSAR models showed statistical significance for the training set and good predictive accuracy for the test set, which strongly manifested the robustness of the CoMFA and HQSAR models. The CoMFA contour maps and the HQSAR contribution maps were both presented. Furthermore, based on the essential factors for ligand binding derived from the QSAR models, sixteen new derivatives were designed and some of them showed higher inhibitory activities confirmed by our models and molecular docking studies. General speaking, this study provides useful suggestions for the design of potential anti-HCV drugs.
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SPED-(Styrene-Polyethyleneglycol Diacrylate-9-Decen-1-ol)- A Novel Resin for Solid Phase Peptide Synthesis; Synthesis and Characterization of Biologically Potent Endothelin Classes of Peptides
M.A. Siyad and G.S. Vinod Kumar
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00050]
Here we present a novel beaded chemically stable, highly permeable hydrophobic/hydrophilic balanced support for solid phase peptide synthesis. The resin (SPED) was prepared by free radical suspension polymerization using monomers styrene and 9-decen-1-ol with amphiphilic cross-linking agent polyethyleneglycol diacrylate (Mn≈ 258). Different cross-linking densities were prepared to check the extent of swelling in different polar and non-polar solvents. The SPED resin was characterized with IR, 13C NMR and surface by SEM. The chemical stability of the support in various peptide synthetic conditions was investigated and monitored by IR spectroscopy. To evaluate the applicability of the new resin in synthetic conditions more challenging peptide sequence of retro-ACP (74-65) was synthesized and compared to commercially available Merrifield resin. The efficiency of SPED was further confirmed by synthesizing biologically important endothelin family of peptides in high yield and purity. The purity of all peptides was checked by RP-HPLC and mass by MALDI-TOF MS.
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Determination of 7,12-Dimethylbenz[a]anthracene in Orally Treated Rats by High-performance Liquid Chromatography and Transfer Stripping Voltammetry
Yavuz Yardım, Abdulkadir Levent, Suat Ekin, Ertuğrul Keskin, Gökhan Oto and Zühre Şentürk
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00051]
A number of polycyclic aromatic hydrocarbons (PAHs) have been shown to be toxicants, and induce carcinogenic and immunotoxic effects. As a model PAH agent, 7,12-dimethylbenz[a]anthracene (DMBA) was the strongest one tested in terms of its biological activities and biotransformation. A new and simple high-performance liquid chromatographic (HPLC) method with diode-array detection at 290 nm was developed and validated for monitoring of DMBA in different matrices (serum, liver and kidney) of rats orally treated with DMBA. Furthermore, the applicability of adsorptive transfer stripping voltammetry (AdTSV) on the pencil-lead graphite electrode to these samples was illustrated using our previously reported data for bulk aqueous solutions of DMBA. HPLC and AdTSV methods, which were compatible with each other, allowed DMBA to be detected down to the levels of 3.82x10-9 M (0.98 ppb) and 6.73x10-9 M (1.73 ppb), respectively. Olive oil solutions of DMBA in dose 50 mg/kg were orally administered. 60 day after a single dose of DMBA, its concentrations in these biological samples from rats were measured by means of both methods. Because of rapid biotransformation, DMBA could not be detected in serum. Only low levels of the compounds were deposited unchanged in kidney whereas its levels were considerably higher in liver. These methods were also applied to the assay whether there is an influence of the intake of aqueous extracts of Hypericum Perforatum L. plant on the parent DMBA levels accumulated in rat tissues.
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A simple and effective approach to the synthesis of isoquinoline derivatives under Solvent-free conditions
Zinatossadat Hossaini, Faramarz Rostami-Charati, Somayeh Firoziyan, Maryam Sabbaghan and Mohammad A. Khalilzadeh
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00052]
An efficient synthesis of dialkyl pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates, pyrrolo[1,2-a]quinoline-1,2-dicarboxylates and indolizines is described via one-pot reactions of isoquinoline, quinoline or pyridine and phenacyl bromids with dialkyl acetylenedicarboxylates or diaryloylacetylene under solvent-free conditions at 50 oC. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods.
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Parallel Microwave-assisted Synthesis of Ionic Liquids and Screening for Denitrogenation of Straight-Run Diesel Feed by liquid-liquid extraction
Miguel A. Cerón, Diego J. Guzmán-Lucero, Jorge F. Palomeque and Rafael Martínez-Palou
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00053]
Seventy-five ionic liquids were efficiently synthesized in parallel format under one-pot, solvent-free microwave-assisted synthesis. These compounds were evaluated as extracting agents of nitrogen-containing compounds from a real Diesel feed before being submitted to hydrodesulfurization process to obtain ultralow sulfur Diesel. Our results showed that halogenated ionic liquids are an excellent alternative due to these compounds are cheaper, present high selectivity for the extraction of nitrogen-containing compounds and can be regenerated and recycled.
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A clean procedure for synthesis of pyrido[d]pyrimidine derivatives under solvent-free conditions catalyzed by ZrO2 nanoparticles
Shahrzad Abdolmohammadi and Saeed Balalaie
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00054]
A simple one-pot method for the preparation of 7-amino-2,4-dioxo-5-aryl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitriles 4 from aromatic aldehydes, malononitrile and 4(6)-aminouracil in the presence of ZrO2 nanoparticles (ZrO2 NPs) as an efficient heterogeneous catalyst is described. The procedure has the advantages of high yields (86-97%), short reaction time (2h) and an environmentally friendly specificity.
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Iodocyclization, Followed by Palladium-Catalyzed Coupling: A Versatile Strategy for Heterocyclic Library Construction
Anton V. Dubrovskiy, Nataliya A. Markina and Richard C. Larock
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00055]
The iodocyclization of functionally-substituted alkynes provides an excellent way to prepare a wide range of iodoheterocycles, which can then be readily elaborated through palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, Hartwig-Buchwald, and carbonylation processes into libraries of medicinally relevant heterocycles. The synthesis of libraries of indoles, benzofurans, benzothiophenes, isocoumarins and pyrones, cyclic imidates, isoxazoles, furans using this approach is reviewed. This technology is very versatile, proceeds under mild reaction conditions in high yields, and tolerates considerable functionality.
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Development and validation of a fluorescence-based HTS assay for the identification of P/Q-type calcium channel blockers
Mario Mezler, David Hermann, Andrew M. Swensen, Andreas Draguhn, Georg C. Terstappen, Gerhard Gross, Hans Schoemaker, Gail Freiberg, Steve Pratt, Sujatha M. Gopalakrishnan and Volker Nimmrich
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00056]
Dysfunction of P/Q-type calcium channels is thought to underlie a variety of neurological diseases. There is evidence that migraine, Alzheimer´s disease, and epilepsy involve a gain-of-function of the channel, leading to abnormal presynaptic vesicle release. P/Q-channel blockers may normalize current flow and consequently lead to an alleviation of disease symptoms. Although the medical need is high, there are no such compounds on the market.
Here we describe a high-throughput screen for P/Q-type calcium channel blockers and the confirmation of hits by automated electrophysiology. We generated a HEK293 cell line stably expressing the α1A subunit of the P/Q-type calcium channel under control of a tetracycline (Tet) promoter. The accessory β1.1 and α2δ1 subunits were co-expressed constitutively. The cell line was pharmacologically characterized by ion channel specific modulators, and revealed functional P/Q-type calcium currents. Using a fluorescence imaging plate reader (FLIPR), an assay for P/Q-type calcium channels was established based on a calcium sensitive dye. High-throughput screening (HTS) of a 150,000 compound-containing sub-library led to the identification of 3262 hits that inhibited the fluorescence signal with potencies below 10 μM. Hit-to-lead (HTL) efforts identified 12,400 analogues. Compounds were clustered into 37 series, and 8 series of interest were prioritized.
An electrophysiological secondary screen, providing a more direct measure of channel function, was implemented into the HTL. 27 selected exemplars of different chemotypes were validated by automated whole-cell patch clamp analysis at inactivated channel state.
The discovery of P/Q-channel blockers may foster the development of new therapeutics for a variety of neurological diseases.
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A High Throughput Scintillation Proximity Imaging Assay for Protein Methyltransferases
Glorymar Ibáñez, David Shum, Gil Blum, Bhavneet Bhinder, Constantin Radu, Christophe Antczak, Minkui Luo and Hakim Djaballah
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00057]
Protein methyltransferases (PMTs) orchestrate epigenetic modifications through post-translational methylation of various protein substrates including histones. Since dysregulation of this process is widely implicated in many cancers, it is of pertinent interest to screen inhibitors of PMTs, as they offer novel target-based opportunities to discover small molecules with potential chemotherapeutic use. We have thus developed an enzymatic screening strategy, which can be adapted to scintillation proximity imaging assay (SPIA) format, to identify these inhibitors. We took advantage of S-adenosyl-L-[3H-methyl]-methionine availability and monitored the enzymatically catalyzed [3H]-methyl addition on lysine residues of biotinylated peptide substrates. The radiolabeled peptides were subsequently captured by streptavidin coated SPA imaging PS beads. We applied this strategy to four PMTs: SET7/9, SET8, SETD2, and EuHMTase1, and optimized assay conditions to achieve Z' values ranging from 0.48 to 0.91. The robust performance of this SPIA for the four PMTs was validated in a pilot screen of approximately 7,000 compounds. We identified 80 cumulative hits across the four targets. NF279, a suramin analogue found to specifically inhibit SET7/9 and SETD2 with IC50 values of 1.9 and 1.1 μM, respectively. Another identified compound, Merbromin, a topical antiseptic, was classified as a pan-active inhibitor of the four PMTs. These findings demonstrate that our proposed SPIA strategy is generic for multiple PMTs and can be successfully implemented to identify novel and specific inhibitors of PMTs. The specific PMT inhibitors may constitute a new class of anti-proliferative agents for potential therapeutic use.
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Discovery and Preliminary SAR of 5-Arylidene-2,2-dimethyl-
1,3-dioxane-4,6-diones as Platelet Aggregation Inhibitors
Abdelaziz El Maatougui, Jhonny Azuaje, Alberto Coelho, Ernesto Cano, Matilde Yañez, Mari Carmen López, Vicente Yaziji, Carlos Carbajales and Eddy Sotelo
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00058]
We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane- 4,6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structureactivity relationships in this series as well as to identify novel derivatives that are up to 60 times more potent than the hit structure 1 and slightly superior to the reference drug Milrinone.
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A support vector machine based method to predict success for polymerase chain reactions
Xiaoqing Yu, Xiaoqi Zheng, Liangyu Meng, Chun Li and Jun Wang
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00059]
Polymerase chain reaction (PCR) is one of the most popular molecular biological techniques and has been widely applied in many areas. However, PCR still faces challenges nowadays. During recent decades, the experimental procedure of PCR, including the primer design, was always the focus of attention, while little attention was paid to the analysis of the PCR template, and still nobody can accurately predict whether or not a DNA sequence can be simply amplified using conventional Taq DNA polymerase-based PCR protocol. In this study, we focus on the DNA template, the subject of PCR experiment, and introduce a support vector machine (SVM) based method to help evaluate PCR result. Through the Jackknife cross-validation test, our method achieves an accuracy of 92.06%, with 93.62% sensitivity and 90.53% specificity.
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PEG-mediated catalyst-free expeditious synthesis of polysubstituted anilines and benzenes via the reaction of malononitrile and β-ketoester derivatives in the presence of activated acetylenes
Mohammad Piltan, Loghman Moradi, Hiwa Salimi, Kiomars Zargoosh and Seyed Amir Zarei
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00060]
Poly(ethylene glycol) (PEG) has been used as a sustainable, non-volatile, and environmentally friendly reaction solvent for synthesis of functionalized anilines and benzenes via the reaction of malononitrile and β-ketoester derivatives in the presence of activated acetylenesat 80°C. No additional solvent and catalyst are required.
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Ganoderma Lucidum Polysaccharides Exert Anti-hyperglycemic Effect on Streptozotocin-induced Diabetic Rats through Affecting β-cells
Jusheng Zheng, Bin Yang, Yinghua Yu, Qi Chen and Tao Huang, Duo L
[FULL-TEXT INQUIRY] [BSP/CCHTS/E-Pub/00061]
Previous studies have demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibited potential anti-hyperglycemic effect in rats. The aim of the present study was to investigate the mechanism of the hypoglycemic effect of a low- molecular-weight Gl-PS in streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats. Gl-PS was extracted and purified from Ganodema lucidum fruiting body. 50 male SD rats were included in the study; 10 were taken as healthy controls; 40 were induced to diabetes by a single injection of 65 mg/kg STZ, of which 30 were selected as successful diabetic rat models. The 30 diabetic rats were divided into three groups: Gl-PS (200 mg/kg Gl-PS), metformin (100 mg/kg metformin) and diabetic control (n = 10 per group). After eight weeks’ oral administration, plasma concentrations of fasting glucose, triacylglyceride, total cholesterol and nitric oxide were significantly decreased in Gl-PS and metformin groups. Pancreatic superoxide dismutase, catalase and glutathione peroxidase were significantly increased in Gl-PS and metformin groups. Histopathological results showed that Gl-PS and metformin had protective effect on β-cells. The mRNA expressions of Bcl-2 and PDX-1 in pancreas were up-regulated, but Bax, iNOS and Casp-3 down-regulated in Gl-PS and metformin groups compared to diabetic control group. The present results suggested that Gl-PS had a hypoglycemic effect in STZ-induced diabetic rats through preventing apoptosis of pancreatic β-cells and enhancing β-cells regeneration.
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