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 13 of 13 for “"Antifolate"”.
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Nuclear PTEN Regulates Thymidylate Biosynthesis and Cellular Sensitivity to Antifolate Treatment
<p>Metabolic reprogramming contributes to tumorigenesis and holds significant promise for cancer therapy. The PTEN tumor suppressor governs a variety of biological processes, including metabolism, by acting on distinct molecular targets in different subcellular compartments. In the cytoplasm, PTEN …
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Folate transport and drug resistance in the African Trypanosome
… of the mechanism of action and resistance of antifolate drugs in African trypanosomes with a specific focus on transport mechanisms. A media deficient in folate and thymidine was established which enabled the assessment of their modulation on antifolate in vitro potencies and also screen a …
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Synthesis of novel 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as selective and potent anti-tumor agents
… (RTX): are a few examples of classical antifolates that are currently in clinical use. Although these compounds are widely used, all of them show dose limiting toxicity due to their non-specific transport into normal cells as well as malignant cells. Currently, clinically used classical …
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Synthesis of furo[2,3-d]pyrimidines, thieno[2,3- d]pyrimidines, pyrrolo[2,3-d]pyrimidines as classical and nonclassical antifolates, receptor tyrosine kinase (RTK) inhibitors and antimitotic agents
… background and research progress in the areas of antifolates, receptor tyrosine kinase (RTK) inhbitors and anti mitotic agents has been discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent …
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Synthesis and translation of novel gram-negative antibacterial agents
… permeation-enhanced sulfonamide drugs––another antifolate antibiotic––have led to cell culture synergy in wild-type P. aeruginosa with single-digit µg/mL concentrations. Furthermore, they have been found to be very well-tolerated orally, inviting further experimentation to flesh out other dosing …
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Single Nucleotide Polymorphisms in the Folypoly-gamma-glutamate synthetase Gene
… Similarly, in the case of cancer chemotherapy, antifolates, such as Lometrexol and Tomudex are retained in cells through the activity of FPGS. Consequently, any single nucleotide polymorphisms (SNPs) that exist in the fpgs gene may decrease or increase the cytotoxicity of antifolates and, …
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Classical Antifolates: Synthesis of 5-Substituted, 6-Substituted and 7-Substituted Pyrrolo[2,3-d]Pyrimidines as Targeted Anticancer Therapies
… research progress in the area of classical antifolates as the targeted anticancer therapies.</p><p> In this study, twelve series of classical 5-, 6- and 7-substituted pyrrolo[2, 3-d]pyrimidines were designed and synthesized. Extensive structure modifications of the pyrrolo[2, 3-d] pyrimidine …
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Design and Synthesis of Pyrimidine Based Fused Heterocyclics in the Potential Treatment of Cancer and Opportunistic Infection
… for PCFT and RFC. PMX, the most widely used antifolate, has three disadvantages: (i) transport by RFC; (ii) dependence on its polyglutamylation for potency; and (iii) development of resistance due to mutagenesis in the target enzyme (thymidylate synthase). This dissertation focuses on the …
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Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates
… background and research progress in the areas of antifolates and antimitotic agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for …
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Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection
… PCFT and RFC.</p> <p>PMX, the most widely used antifolate has three disadvantages: (i) transport by RFC; (ii) dependence on its polyglutamylation for potency; and (iii) development of resistance due to mutagenesis in the target enzyme (thymidylate synthase). This dissertation focuses on …
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Structural examination of trypanosomatid tubulin-binding cofactors and pteridine reductase 1 inhibition
… reducing the therapeutic action of traditional antifolate molecules in these organisms. Inhibition of PTR1 is therefore desirable from a drug discovery viewpoint. The crystal structure of Leishmania donovani PTR1 was determined using data extending to 2.5 Å resolution with a view to generating …
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Discovery of Pyrimidine-based Heterocycles as Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment of Cancer
<p>This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor …
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Synthesis of 2,4,6-Substituted Pyrrolo[2,3-d]pyrimidines as Potential Anticancer Agents
… and work have been done in the areas of antifolates development, such as folate function, its three uptake mechanisms inside human cells, antifolates’ role in chemotherapy, <em>et. al</em>. In addition, the Structure-Activity-Relationship design rationale for the series of antifolates …