Digital Commons Network^™

Synthesis Of Bioactive Heterocycles, Shaila Akter Shetu

Theses and Dissertations

The Discovery of a variety of heterocyclic drugs for the treatment of cancer and other diseases (e.g, neglected tropical diseases) is a medical breakthrough and inspiring for the research community as a whole. A wide range of natural, semi-synthetic, and synthetic anticancer drugs are synthesized using various methods. Among them, β -lactams stand out as a novel class of antibiotics that has different types of biological as well as anti-cancer properties. β -lactam has become a premier and active research subject towards the development of revolutionary anti-cancer drugs. In recent years, a large amount of investigations have been done to …

Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias

Theses and Dissertations

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …

Total Synthesis Of Cytotoxic Mansouramycins From Amino Acids, Beatriz Gamez

Theses and Dissertations

Natural products produced by plants, animals, and microorganisms are of significant importance in chemistry for being major sources of molecular scaffolds essential for new drug discovery. Mansouramycins are cytotoxic bioactive compounds containing isoquinoline skeletons with substituents on the quinone and pyridine rings that may be difficult to synthesize. Synthetic processes exist for compounds B and D, however, there exists an absence of simple synthetic approaches to all four alkaloids.

This project aims to provide a general total synthetic pathway to Mansouramycins A—D from amino acids for possible use in cancer treatment via these isoquinolinequinones. Preliminary experimentation suggests there may be …

Chemical Modification And In Silico Validation Of Medicinally Privileged Molecular Scaffolds As Kras And Sars-Cov-2 Protease Inhibitors, Precious M. Okwuchukwu

Theses and Dissertations

Coronavirus disease was declared a global pandemic by WHO in March 2020, cancer is the second leading cause of death by a disease. Several scientists around the world are working relentlessly to discover an effective remedy to eradicate these deadly diseases. A natural polyphenol (magnolol) has been isolated from a tree Magnolia grandiflora (family Magnoliaceae) found on UTRGV campuses. This research is focused on design of a series of chemically modified sulfonyl derivatives based on the isolated magnolol framework and other medicinally privileged molecular scaffolds framework that can effectively bind to the COVID-19 main protease, SARS- CoV-2 3CL protease …

Analysis Of The Functional Relationship Of Protein Kinase Families Using Phospho-Proteomics Data, David A. Parra Peña

Theses and Dissertations

As cancer research advances, Mass-spectrometry based proteomics is becoming a widely used technique for proteome characterization. Phosphoproteomics is a specific type of proteomics that characterizes proteins with the reversible post-translational modification of phosphorylation PTM), which has allowed the identifications of thousands of phosphorylation sites. These phosphorylation sites, also known as substrates, are known to interact with a protein type named kinases. Studies have shown that abnormal phosphorylation activity is related to cancer diseases. Moreover, these kinases are divided into families, based on the similarity of their catalytic domain, as this part of their amino acid sequence determines a large part …

Genetic Analysis Of Pi3k And Mtor Inhibition In U87mg Glioblastoma Cell Line, Carl G. Litif

Theses and Dissertations

NVP-BEZ235 is a Glioblastoma Multiform chemotherapeutic dual PI3K/mTOR pathway inhibitor created in 2008 and has since been proven experimentally to induce pluripotentcy in oncological cell populations. The inhibition of PI3K and mTOR has shown to coerce phenotypes associated with stem cell markers, most notably OCT4. It is necessary to understand the genetic composure of how PI3K/mTOR inhibited tumor cells are bypassing the canonical pathway for proliferation and growth and utilizing other parallel sources for tumor invasion into other neural regions. Taking a genetic approach with RNA-sequencing allowed us to gain insight into how glioblastoma interact with cytoskeleton factors MAPK4 and …

Investigating The Localization Of Foxo Transcription Factors In Glioblastoma, Leetoria Hinojosa

Theses and Dissertations

The Phosphatidylinositol 3 Kinase (PI3K) pathway is an essential intracellular signaling pathway that regulates cellular growth, survival, and fate. Canonically, the activation of this pathway removes forkhead box subfamily O transcription factors (FOXO -1, -3, and -4) from the nucleus. However, in cancer cells such as glioblastoma multiforme, FOXO factors are at least in part nuclear despite the activation of the PI3K pathway. Previous research indicated that FOXO3 localization was not affected when the pathway was inhibited in breast cancer cells, which challenged the conventional paradigms for FOXO factor regulation. Therefore, we were interested in investigating the nuclear localization of …

Investigating The Role Of Nuclear Foxo3 In Pten-Null Glioblastomas, Lilia Sanchez

Theses and Dissertations

The PI3K pathway activates AKT, leading to inactivation of FOXO transcription factors. Loss of PTEN results in constitutive inactivation of tumor suppressor FOXO. There is increasing evidence that FOXO resides and promotes transcriptional activity in the nucleus despite high PI3K output within certain advanced cancers and embryonic stem cells. Here, we investigate the regulation and roles of FOXO transcription factors in glioblastoma and basal breast cancer. First, we built and published genetic models to investigate the roles of FOXO transcription factors in cancer cell lines for glioblastoma (U87MG). We examined the function of FOXO transcription factors using these genetic models …

Metabolic Dysregulation: An Investigation Of The Role Of Foxo3 In Gluconeogensis In Pten-Null Glioblastomas, Victor Fanniel

Theses and Dissertations

Many processes are regulated by the Phosphatidylinositol 3 kinase (PI3K) pathway in the cell including cell survival, metabolism, and apoptosis. Increased activation of the PI3K pathway is a hallmark of many cancers which can be oftentimes attributed to the mutation of PTEN, which encodes an enzyme that performs the reverse reaction of PI3K. When PTEN is null-mutated, this creates a constitutively active PI3K pathway and constitutively active AKT. Since AKT phosphorylates conserved residues on FOXO transcription factors to mark them for nuclear export, this renders FOXO inactive. However, new research has provided evidence that FOXO is still present in …