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Synthesis Of 2,4,6-Substituted Pyrrolo[2,3-D]Pyrimidines As Potential Anticancer Agents, Si Yang

Electronic Theses and Dissertations

This thesis mainly focuses on the introduction of the background 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, et. al. In addition, the Structure-Activity-Relationship design rationale for the series of antifolates will also be discussed. Nevertheless, the details of synthesizing these pyrrolo[2,3-d]pyrimidines as potential antifolates have been described, including chemistry reviews on the pyrrolo[2,3-d]pyrimidine scaffold, and the challenges encountered and the solutions how to solve or improve in order to achieve better yield.

Targeting The Major Regulator Of Mitosis., J. Mason Hoffman

Electronic Theses and Dissertations

Mitosis-inhibiting chemotherapeutics (e.g. taxanes) are frequently used to treat multiple cancer types. Recently, there has been much concern about the limited success of these drugs due to resistance and a lack of molecular targets. Thus, there is high demand for new drugs with diverse cellular targets. Targeting the regulators of mitosis is a promising approach. The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle progression at multiple points. The interaction of ANAPC2 and ANAPC11, catalytic core subunits, is necessary for APC/C function. An in silico approach was used to identify compounds predicted to prevent assembly …

An Analysis Of Neurogenesis In A Mouse Model Of Chemotherapy Related Cognitive Impairment, Maxwell A. Hennings

Electronic Theses and Dissertations

Cancer patients treated with adjuvant chemotherapy often experience cognitive decline following treatment. This phenomenon, often dubbed “chemo brain” or “chemo fog” is usually temporary, but for a subset of survivors, these cognitive impairments can be long-lasting (>10 years) and negatively affect patients’ quality of life, career performance, and social fulfillment. While it is unclear what neurobiological mechanisms underlie chemotherapy related cognitive impairment, the majority of the animal literature has focused on adult neurogenesis. One process important for neurogenesis is the proliferation of new neurons within the dentate gyrus of the hippocampus. It is evident that many chemotherapy agents can …

Inhibition Of Chemotherapeutic-Induced Apoptosis In Esophageal Squamous Cancer Cells By The Keystone Periodontal Pathogen, Porphyromonas Gingivalis., Atul Kumar Agrawal

Electronic Theses and Dissertations

Recent evidence has shown that P. gingivalis, a Gram-negative, anaerobic oral bacterium, is negatively associated with the presence and outcome of esophageal squamous cell carcinoma (ESCC). While potential underlying mechanisms are yet to be established, P. gingivalis infection is known to inhibit apoptosis in gingival epithelial cells. Therefore, we hypothesized that P. gingivalis may also inhibit of the induction of apoptosis in human ESCC cells exposed to the commonly employed anti-ESCC chemotherapeutic agent, cisplatin. The capacity of P. gingivalis, at variant multiplicities of infection, to suppress cisplatin-induced necrosis and apoptosis in EC9706 ESCC cells was established by lactate …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

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 targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …