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Search for "high-throughput screening" in Full Text gives 44 result(s) in Beilstein Journal of Organic Chemistry.
Computational methods in drug discovery
Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267
- methods are discussed. Advances in virtual high-throughput screening, protein structure prediction methods, protein–ligand docking, pharmacophore modeling and QSAR techniques are reviewed. Keywords: ADME; computer-aided drug design; docking; free energy; high-throughput screening; LBDD; lead optimization
- the consumer market. Approximately 75% of the cost is due to failures that happen along the drug discovery and design pipeline [1]. Nowadays with faster high-throughput screening (HTS) experiments, which can assay thousands of molecules with robotic automation, human labor associated with screening of
- it possible to use structure-based tools such as virtual high-throughput screening and direct docking methods on targets and possible drug molecules. The affinity of molecules to targets can be evaluated by computing various estimates of binding free energies. Further filtering and optimization of
Profluorescent substrates for the screening of olefin metathesis catalysts
Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203
- have been prepared and tailored towards specific applications [12]. With the ultimate aim of identifying new olefin metathesis catalysts using high-throughput screening, we set out to develop and evaluate olefinic substrates amenable to a 96-well plate screening format. Results and Discussion A quick
Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions
Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186
- high; (iii) each substrate might result in many different oxidation products. Here, we describe how such issues can be overcome by (i) using surrogate high-throughput screening (HTS) protocols that can deal with a large number of mutants; (ii) identification of active mutant libraries; (iii
A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime
Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275
- inhibitors [17][18][19][20][21]. Another powerful area, yet a somewhat less utilised role for fluorine is as a tag for 19F NMR that offers several analytical advantages including speed, sensitivity and selectivity [22][23]. Fluorinated molecules have served as valuable 19F NMR probes in high-throughput
- screening, drug metabolism and protein binding experiments as well as in assessing gene expression [24]. Nevertheless, the preparation of 3-trifluoromethyl-2-isoxazolines 1 has not been extensively studied so far. In the literature only a few examples of the preparation of these derivatives through a
Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties
Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259
- inducers represents an attractive approach for the discovery of new anticancer agents. 1,2,4-oxadiazole A (Figure 2) was found to act as an apoptosis agent by a high-throughput screening (HTS) assay [8]. A series of 1,2,4-oxadiazole-5-carboxamides B have been synthesized and tested as inhibitors of the
ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans
Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171
- frontline treatments. This, in turn, affords critical lead-time towards the development of novel antimicrobial drugs. The National Institutes of Health Molecular Libraries and Probe Production Centers Network (NIH-MLPCN) recently performed a high-throughput screening (HTS) campaign to search for potential
- against diverse mechanisms of fluconazole resistance, including biofilm formation, drug-target mutations, and efflux-pump amplification. Conclusion High-throughput screening of 300,000 compounds from the NIH’s MLSMR collection identified several substances that potentiate the effect of fluconazole in
Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway
Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103
- . Importantly, none of the probes showed evidence of cytotoxicity in immortalized human hepatocyctes (Fa2N-4 cells) and in the NCI-60 cell line cytotoxicity panel with 10 and 50 μM test concentrations [36]. Conclusion The high-throughput screening of cell-based phenotypic and specific NOD1 protein-based assay
Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)
Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82
- binding of TDP-43 to nucleotides. Cassel et al. [42] developed a high-throughput screening assay whereby TDP-43 nucleotide binding could be assessed. A screen of 7360 compounds yielded a series of small molecules that disrupt oligonucleotide binding to TDP-43 protein [42]. Later, this series of 4
- protein aggregation. Top: selected compounds identified in high-throughput screening. Bottom: advanced compounds. Compounds identified by Nowak and co-workers [37] in silico that selectively bind SOD1 over human plasma and inhibit A4V-SOD1 aggregation
- come from animal studies demonstrating that the reduction of SOD1 protein levels in motor neurons causes these cells to become resistant to ALS-induced cellular death [23]. In order to identify small molecules that downregulate the transcription of SOD1, Murakami et al. [24] developed a high-throughput
From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies
Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31
- step involves the use of a β-amino acid-forming three-component reaction (3CR), the scope of which defines its role in the synthetic strategy. Keywords: β-amino acid; benzimidazole; multicomponent reaction; Introduction Library syntheses and high-throughput screening can often be combined to enable
Asymmetric synthesis of host-directed inhibitors of myxoviruses
Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23
- University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA 10.3762/bjoc.9.23 Abstract High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead
- principle, less susceptibility to the development of resistance. Using high-throughput screening, in combination with counter-screening for detecting a broadened viral target spectrum that extends to other pathogens of the myxovirus families, our research group has been successful in identifying small
Automated three-component synthesis of a library of γ-lactams
Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206
- ; maleimide; organocatalysis; parallel synthesis; reductive amination; Introduction In recent years, the rapid access to structurally diverse and complex small molecules has grown in importance within the context of high-throughput screening of biologically relevant targets. The need for such compounds, both
Exploring chemical diversity via a modular reaction pairing strategy
Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147
- demonstrate interesting behavior in biological screening. To gauge these prospects rigorously, these compounds have been submitted for evaluation of their biological activity in high-throughput screening assays at the NIH MLPCN and the results will be reported in due course. Biologically active benzofused
Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41
Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130
- , ranging from diverse peptides isolated from different natural sources to synthetic peptides generated with high-throughput screening methods. From this large sample size, a number of characteristics have been identified that all contribute to the antimicrobial potency of these polypeptides. In this study
Parallel solid-phase synthesis of diaryltriazoles
Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115
- method may find application in the combinatorial search for selective protein–protein inhibitors. To that end, most of the compounds prepared herein were submitted to the Molecular Libraries Small Molecular Repository for ongoing inclusion in high-throughput screening activities. Experimental General
Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent
Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182
- effect of this OP on AChE was estimated by using a fully automated high-throughput screening assay recently developed for the characterization of potential nerve agent detoxifying materials [43]. This test involves incubation of the nerve agent with an excess of a respective cyclodextrin derivative at
Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope
Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173
- high-throughput screening protocol for evaluating chimeric, self-sufficient P450 biocatalysts and their mutants against a panel of substrates was developed, leading to the identification of a number of novel biooxidation activities. Keywords: biocatalysis; C–H activation; high-throughput screening
- , often with high regio- and stereoselectivity [1], and are therefore attractive candidates for biocatalyst development. However, the need for reconstitution of protein redox partners, the necessary use of expensive NAD(P)H, and the lack of widely applicable high-throughput screening protocols render the
- whole-cell P450 systems would be amenable to incorporation into a high-throughput screening protocol in multiwell plates. Figure 1 outlines the design of the screening platform: E.coli hosts containing a variety of easily engineered chimeric constructs are incubated with the substrate under
Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor
Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111
- evaluation, the compounds targeting HCV replication being the most promising candidates to achieve a sustained virological response [1][4]. Several years ago, a high-throughput screening of the GlaxoSmithKline compound collection identified a series of small pyrrolidine molecules, e.g., 1 (Figure 1), able to
Asymmetric reactions in continuous flow
Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19
- reproducibility due to the precise control over reaction conditions in these devices. Continuous flow technology has excellent potential for the integration of a high level of automation and for the incorporation of on-demand reaction analysis. This can be advantageous for applications such as high-throughput
- screening and synthesis, as well as for the continuous production of significant quantities of compound at higher efficiency and lower costs [1][2][3][4][5][6][7][8]. Stereoselective transformations are among the many different classes of reactions that have been investigated using continuous flow
Mixtures of monodentate P-ligands as a means to control the diastereoselectivity in Rh-catalyzed hydrogenation of chiral alkenes
Beilstein J. Org. Chem. 2005, 1, No. 3, doi:10.1186/1860-5397-1-3
- libraries of chiral metal complexes or metal-free catalysts[9] followed by medium- or high-throughput screening.[5] Catalyst diversity is achieved by the design and synthesis of modular ligands comprised of several building blocks which can be varied at will and easily assembled covalently. Another strategy
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