Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 43 for “"hit compounds"”.
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Identification of potential antibiofilm hit compounds from two African natural product database against multi-drug resistant staphylococcus aureus: an in silico study
… data. The complex chemical diversity of natural compounds makes them a reservoir of bioactive molecules for drug discovery. This study seeks to identify effective potential antibiofilm compounds from a query dataset compiled from two African natural product databases (SANCDb and AfroDb). A …
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Novel Modulators of Human Sperm Motility
… assay (HTS) of 3312 drug discovery ion channel compounds was performed. The screen identified 14 hit compounds that increase intracellular calcium in human spermatozoa. This project investigated these compounds, along with, 6 hit compounds previously identified from a HTS of a Chemogenomics …
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Early-stage drug discovery of HIV-1 frameshifting modulators
… was conducted. The initial screening triage of hit compounds led to the selection of several false positives due to auto-fluorescent compound properties. I subsequently re-designed the screening cascade to incorporate a counter-screen that was effective at eliminating false positives. …
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Design, Synthesis, and Structure-Activity Relationship Investigation of Selective Sphingosine Kinase Inhibitors
… potency was tested in a broken-cell assay, and hit compounds were further evaluated in a yeast cell assay to determine EC50 values. The U937 cell line and mice model were utilized for hit compounds to quantify S1P reduction in vitro and in vivo. Our preliminary results indicated compound 2.14d …
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Characterizing the Activity of Three Novel Differentiation-Inducing Compounds in Neuroblastoma Cells
… three novel neurite-inducing small molecules (Compounds 3, 4, and 10) were identified. The objective of my study is to determine whether the hit compounds have a generic differentiation-inducing effect in neuroblastoma cells with different genetic backgrounds, and whether that the induced cell …
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Xenopus laevis as a chemical genetic screening tool for drug discovery and development.
… towards the treatment of melanoma cancer. 13 hit compounds identified were shown to have significantly lower IC50’s in the A375 melanoma cell line when compared to two control cell lines. Using the structural data of compounds screened (combined with the phenotypic data generated by the …
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HIGHLY SPECIFIC FLUORESCENT PROBE FOR MOUSE PLURIPOTENT STEM CELLS
… for mESC via high throughput screening of compounds. The hit compound was named CDy9. High throughput screen found 23 hit compounds that are specific to mESC. The cell panel test identified CDy9 as the most specific compound. FACS sorting of CDy9 treated co culture of mESC and MEF proved …
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Characterization of an Evolving Serotonin Transporter Computational Model
… small molecule structural library. Selected VS "hit" compounds were procured and tested in vitro; encouragingly, two compounds with novel structural scaffolds bound SERT with modest affinity. The combination of computational modeling, site-directed mutagenesis and pharmacologic characterization …
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Compounds Modulating Calcium and Motility in Human Spermatozoa
… as a surrogate for motility, identified 10 hit compounds from the UoD DDU Selleck MIH prescribables library that induced an increase in [Ca2+]i in human spermatozoa in-vitro. This thesis investigated the effect of this [Ca2+]i using techniques including CASA, Kremer tests and Flow cytometry …
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Synthesis of bespoke matrices to investigate a novel anti-tumour molecular target using affinity chromatography. The design, synthesis and evaluation of biotinylated biarylheterocycles used as novel affinity probes in the identification of anti-tumour molecular targets.
… independent of duplex DNA binding affinity. The compounds were tested in the NCI 60-cell line panel and COMPARE analysis suggests they have a novel mechanism of action, targeting the product of a ¿gene-like sequence¿ of unidentified function. The identity of likely protein targets was explored …
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Chemical Tools to Monitor and Inhibit poly(ADP -Ribosyl)ation
… it has been difficult to intelligently design compounds to inhibit this enzyme. To date, the known inhibitors of PARG can be predominantly grouped into the three categories of DNA intercalators, tannins, and ADP-ribose analogues. While these compounds have proven valuable in the in vitro …
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Discovery of Novel Glycogen Synthase Kinase-3beta Inhibitors: Molecular Modeling, Virtual Screening, and Biological Evaluation
… To identify structurally novel and diverse compounds that effectively inhibit GSK-3â, we performed virtual screening by implementing a mixed ligand/structure-based approach, which included pharmacophore modeling, diversity analysis, and ensemble docking. The sensitivities of different …
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Novel Neuroblastoma Differentiating Agents
… screening (HCS) was conducted to identify hit compounds. This screening measured neurite outgrowth, a phenotypic change which has been described as a marker of differentiation in neuroblastoma cell lines. From this screening, three hits that induced the desired changes in cancer cells were …
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Design and Synthesis of Covalent Inhibitors as Novel Anti-Infective Compounds
… inhibited.<br/><br/>Finally, some of the hit compounds identified by screening the covalent fragment library against these targets were selected and further developed with the goal of increasing potency and selectivity (Chapter 5).
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Studies within Fragment-Based Drug Discovery: Library Synthesis and Hit-to-Lead Optimisation
… from Pseudomonas aeruginosa identified several hit compounds based on an indole unit. Synthetic efforts were undertaken to elaborate these fragment hits to increase potency. The adopted strategy focused on growing the indole fragment towards the nearby oxaloacetate binding pocket and occupying …
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Investigation of O-acetylserine sulfhydrylase enzymes from bacterial pathogens as potential drug targets
… inhibitors. Virtual screening produced five hit compounds that were tested in vitro, giving compound 5 with inhibition in the mid micromolar range. Analysis of compound 5 docking indicates interactions with the NgCysK active site residues through hydrogen bonds and supporting hydrophobic …
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Development of biophysical and Mass Spectrometry Assays for APOBEC3 cytosine deaminases: discovery and validation of cnvalent and non-covalent ligands
… of non-specific thiol binding of covalent compounds. The assay, termed ALARM MSPS (A La Assay to detect Reactive Molecules via Mass Spectrometry Peptide Sequencing), can be utilized to measure any covalent compound and its non-specific protein thiol reactivity through isotopic labeling. …
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Assays for lycosyltransferases
… for screening two compound libraries (c. 400 compounds in total) against LgtC for the first time. Positive hits were identified from both screening campaigns and selected compounds from two structural classes were characterised. One of these inhibitor classes was identified as molecular …
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Computational Methods to Identify and Target Druggable Binding Sites at Protein-Protein Interactions in the Human Proteome
… of interface residues for the identification of hit compounds from structure-based virtual screening. The tight uPAR•uPA interaction offers a platform to test methods that leverage hot spots on both the protein receptor and ligand. A method is described that enriches for small molecules that both …
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Computational Ligand-Based CNS Therapeutic Design: The Search for Novel-Scaffold Norepinephrine Transporter Inhibitors
… software. A group of four structurally-diverse compounds with high NET binding affinities comprised the training set used to generate the model. A test set, which included ten compounds with a range of known NET affinities, served in the validation of the model. The constructed pharmacophore …
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