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 25 for “"in silico screening"”.
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Design, Synthesis and Biological Evaluation of Inhibitors of Polysialyltransferases PST and STX. Design, synthesis and biological evaluation of a range of N-modified mannosamines, sialic acids and analogues from in silico screening as inhibitors of PolySia-NCAM biosynthesis with anti-migration activity.
… NCAM (polySia-NCAM) is re-expressed in a number of tumours, including small cell lung carcinoma and neuroblastoma and is strongly associated with aggressive, invasive and metastatic tumours in the clinic. SiRNA knockdown of the polysialyltransferases (polySTs), the enzymes responsible …
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Computer-Aided Drug Design and Discovery, Screening and Synthesis of Small Molecule Inhibitors of Nucleoside Transporters
<p>Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined …
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Design, Synthesis, And Evaluation Of Molecular Inhibitors For Biologically Relevant Enzymes
<p>The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The …
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Small Molecule Modulation of the Cell Cycle: Discovery of Anticancer Compounds That Induce G1- and M-Phase Cell Cycle Arrest and Characterization of Their Modes of Action
… targets of bioactive small organic molecules remains a significant challenge in modern biomedical research and drug discovery. This dissertation details two phenotype-based discovery projects. Chapter 1 highlights the importance of the identification of new bioactive small molecules in drug …
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Rational development of novel small molecule leads against the transcriptional activator protein ExsA of Pseudomonas aeruginosa
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen. It is present in aquatic, marine, and soil environments and can also be found in a variety of anthropological environments, including water distribution systems and hospitals. This prevalence is concerning due to P. aeruginosa’s …
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Investigating the nuclear import protein KPn߀1 as a cancer therapeutic target
… and progression of cancer, many of which are being investigated as potential therapeutic targets. Previous work in our laboratory and others reported the elevated expression of the nuclear import protein Karyopherin Beta 1 (Kpnβ1) in various cancers. The inhibition of Kpnβ1 by siRNA silencing …
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Computationally-Derived Design Principles for Water Oxidation Catalysts
… need to be discovered to enable its use at the industrial scale. The most active known water oxidation catalysts (WOCs) follow a common theme in chemical catalysis, relying on rare metals such as ruthenium and iridium. To discover alternatives that retain this level of activity while instead …
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Hijacking Cancer Signaling: First-in-class JPRK-targeting Ligands for Fibrolamellar Hepatocellular Carcinoma
Described herein is a drug screening project focused on an oncoprotein beginning with in silico fragment screening against an un-drugged target and concluding with a collaboration to evaluate single digit nanomolar potent and >500-fold selective drug candidates in patient derived xenografts. …
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Development of biophysical and Mass Spectrometry Assays for APOBEC3 cytosine deaminases: discovery and validation of cnvalent and non-covalent ligands
APOBEC3 enzymes are cytosine deaminase enzymes that catalyze the conversion of a cytosine base to uracil in single-stranded DNA. There are seven members of the APOBEC3 family – A3A/B/C/DE/F/G/H. APOBEC3 proteins are a part of the innate immune defense system against viral infection, and mutate the …
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Design and Synthesis of Novel Small Molecule Drugs for the Treatment of Cancer and Osteoporosis
… the world which poses major health threat. In this thesis, we provide the background information to two types of cancers, namely ovarian cancer and liver cancer, as well as osteoporosis, and our approach for the treatment of the diseases. In chapter one, we discussed the background …
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Preclinical Investigation of Mitochondrial Fission Inhibitors in Pulmonary Arterial Hypertension and Non-Small Cell Lung Cancer
Background: Dynamin-related protein 1 (DRP1)-mediated mitochondrial fission is coordinated with nuclear division. This phenomenon, known as mitotic fission, is increased in hyperproliferative diseases, such as non-small cell lung cancer (NSCLC) and pulmonary arterial hypertension (PAH), due to …
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Structural analysis of LMO2 for the development of a small molecule inhibitor
LMO2 is a nuclear LIM-only protein encoded by a gene located on chromosome 11p13 and was originally discovered through its activation due to specific chromosomal translocations in patients with T-cell acute lymphoblastic leukaemia (T-ALL). The specific chromosomal translocations occur with either …
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Discovery and evaluation of novel and characterised bacteriocins for future applications
Bacteriocins are a heterogeneous group of small, ribosomal-synthesised, antimicrobial peptides produced by bacteria, capable of inhibiting bacteria both closely related or indeed those from other genera than the producer. These peptides are often active in the nanomolar range making them highly …
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Application of foundation models for molecular representation in cancer drug discovery and precision oncology
Drug discovery is a resource-intensive and time-consuming process, often requiring decades of effort and substantial financial investment, with a high risk of failure. Despite advances in high-throughput screening technologies, the size of chemical space presents a significant challenge: it is not …
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Genomics approaches to exploit the biotechnological potential of marine sponge-derived Streptomyces spp. isolates
… genus are widely known for their capability in producing compounds of pharmacological, clinical, and biotechnological interest, being the source of approximately a third of all the antibiotics that have been identified to date. However, the discovery of natural products with antimicrobial …
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Molecular design of interfacial modifications to alter adsorption/desorption equilibria at fluid-adjoining interfaces
The thermodynamics and mass transfer kinetics of adsorption and desporption at interfaces play vital roles in chemical analysis, separation processes, and many natural phenomena. In this work, computer simulations were used to design interfacial modifications to alter the physical processes of …
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Identification and Characterization of the Mechanisms of Action of Novel Antiviral Compounds Targeting the Minimal Replication-Transcription Complex of SARS-CoV-2
After its emergence in 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified as the etiologic agent of COVID-19, a potentially fatal respiratory illness in Wuhan, China, which rapidly spread to the entire world. The pandemic has had dramatic economic, social and …
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Structure-based development of novel chemical scaffolds as inhibitors of the store-operated calcium entry pathway
Calcium (Ca2+) is an intracellular messenger regulating various physiological activities. The ‘store-operated calcium entry’ (SOCE) is a significant, almost ubiquitous Ca2+ signaling pathway and is triggered when intracellular Ca2+ stores (e.g., endoplasmic reticulum, ER) are depleted, either …
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Identifying circulating biomarkers in a cohort of hypercholesterolaemic patients with statin intolerance from Gauteng, South Africa
Cardiovascular disease is one of the leading causes of death worldwide. Dyslipidemia, defined by high circulating levels of atherogenic apoB-containing lipoproteins, contributes significantly to the increasing burden of cardiovascular morbidity and mortality. At public health care institutions, in …
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