Physical Sciences and Mathematics Commons^™

Ionic Liquids And Gumbos For Biomedical And Sensing Applications, Paul Kipkorir Sang Magut

LSU Doctoral Dissertations

This dissertation is a synopsis of advancements in the field of ionic liquids and a group of uniform materials based on organic salts (GUMBOS) in biomedical applications, especially with regard to cancer research. The toxicity of chemotherapeutic agents to normal tissues and drug resistance are a major concern in cancer treatment. In this dissertation, GUMBOS and nanoGUMBOS as well as ionic liquids and nanodroplets are explored as possible chemotherapeutic agents with minimal toxicity to normal cells. In the first part of my dissertation, exploitation of ionic liquid chemistry to modulate toxicity of rhodamine 6G is reported. Rhodamine 6G-based GUMBOS with …

Synthesis Of Ester Derivatives Of Resveratrol As Potential Anti-Cancer Drugs, Parasmani Pageni

Electronic Theses and Dissertations

Resveratrol is a naturally occurring phytoalexin of the stilbene family produced by various plants in response to stress, UV radiation, and fungal attack. It is primarily found in peanuts, berries, grape skin, and red wine. Resveratrol has been found to exhibit anti-cancer, anti-inflammatory, anti-aging, and anti-oxidant properties. Research indicates that diets enriched with resveratrol containing substances result in less incidence of cancer. Unfortunately, the low bioavailability and solubility has been a huge setback for its potential prospects. As a result, efforts have been made to synthesize derivatives of resveratrol with increased solubility and bioavailability. Three triester novel resveratrol derivatives 3, …

Protein-Protein Interaction Between Multi-Functional Protein Cad And Protein Phosphastase 1 (Pp1), Meenal Mhaskar

Master's Theses and Doctoral Dissertations

Uncontrolled cell proliferation, a hallmark of cancer, is associated with activation of CAD, a multifunctional protein that catalyzes the first three steps in pyrimidine biosynthesis. The cell cycle dependent regulation of pyrimidine biosynthesis is a consequence of sequential phosphorylation of CAD Thr-456 and Ser-1406 by the MAP kinase and PKA cascades, respectively. The mechanism that controls the timing of these events is not well understood. Our hypothesis is that timing of the activation and nucleocytoplasmic dynamics of CAD is controlled by signaling complexes with kinases and phosphatases. Interestingly, a consensus sequence for PP1 targeting proteins is located immediately adjacent to …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Virtual Screening For Inhibitors Of Anti-Apoptotic Proteins: Dck, Bcl-Xl, Mcl-1, Mdmx, And Mdm2, Courtney Jerome Du Boulay

USF Tampa Graduate Theses and Dissertations

←Within this dissertation the topic of virtual screening is discussed with regard to three different cancer targets and also a brief introduction of the tools used in virtual screening. In Chapter 1, the reader will be introduced to virtual screening and the programs that are used in virtual screening. In Chapter 2, the first of three projects are discussed. This project consists of the work that was done to find inhibitors of the P53 binding domain of MDMX. In this project the mobility of residues within the binding site of MDMX are discussed and the ways in which we attempted …

Polymer Microsystems For The Enrichment Of Circulating Tumor Cells And Their Clinical Demonstration, Joyce W. Kamande

LSU Doctoral Dissertations

Cancer research is centered on the discovery of new biomarkers that could unlock the obscurities behind the mechanisms that cause cancer or those associated with its spread (i.e., metastatic disease). Circulating tumor cells (CTCs) have emerged as attractive biomarkers for the management of many cancer-related diseases due primarily to the ease of securing them from a simple blood draw. However, their rarity (~1 CTC per mL of whole blood) makes enrichment analytically challenging. Microfluidic systems are viewed as exquisite platforms for the clinical analysis of CTCs due to their ability to be used in an automated fashion, minimizing sample loss …

Allosteric Regulation Of Caspase-6 Proteolytic Activity, Elih M. Velazquez-Delgado

Open Access Dissertations

Caspases are cysteine proteases best known for their controlling roles in apoptosis and inflammation. Caspase-6 has recently been shown to play a key role in the cleavage of neurodegenerative substrates that causes Huntington and Alzheimer's Disease, heightening interest in caspase-6 and making it a drug target. All thirteen human caspases have related specificities for binding and cleaving substrate, so achieving caspase-specific regulation at the active site has been extremely challenging if not impossible. We have determined the structures of four unliganded forms of caspase-6, which attain a novel helical structure not observed in any other caspases. In this conformation, rotation …

Detection Of Folate Receptor From Fr+ Cells, Gopikrishna Pinnaka

All Capstone Projects

Targeted drug delivery is a newer and less explored arena that has potential scope in tumor targeting because the regular chemotherapy has lethal effects on the normal cells also. Our present Work was an attempt to specifically target receptors on cancerous cells, especially the Folate Receptor (FR). Folate is important for cells for DNA synthesis and the tissues that rapidly divide require folate, cancer cells are no exceptions for this. To cope with the increased demand for the folate the cancer cells express greater FR on the cell surface. This very fact was our basis for the construction of our …

Design, Synthesis, And Biological Evaluation Of Novel Polyamine Transport System Probes And Their Application To Human Cancers, Aaron Muth

Electronic Theses and Dissertations

The mammalian polyamine transport system (PTS) has been of interest due to its roles in cancer and maintaining cellular homeostasis. Polyamines are essential growth factors which are tightly controlled via a balance of biosynthesis, metabolism, import, and export. This work focused on the development and biological testing of polyamine transport probes to help understand the molecular requirements of the PTS. This was mediated through the use of a CHO (PTS active) and CHO-MG* (PTS deficient) screen, where compounds demonstrating high toxicity in CHO and low toxicity in CHO-MG* were considered PTS selective. The first chapter focused on the development of …

Synthesis Of Resveratrol Ester Derivatives Using Selective Enzymatic Hydrolysis., Marian Osei-Mensah

Electronic Theses and Dissertations

Resveratrol, a naturally derived stilbene, is an interesting compound mostly talked about recently because for its anti-cancer properties. Unfortunately it has some shortcomings due to its low bioavailability and low solubility in water. For this reason, my research is to overcome resveratrol's drawbacks by improving its bioavailability and hydrophilicity. My research is focused on syntheses of novel derivatives of resveratrol such as 3, 5-di-O-isobutyroyl resveratrol and 3, 5-di-O-hexanoyl resveratrol using lipase catalyzed hydrolysis. Therefore, the tri-acylated resveratrols 3, 5, 4'-tri-O-isobutyroyl resveratrol and 3, 5,4'-tri-O-hexanoyl resveratrol were first synthesized.

3,5,4'-tri-O-isobutyroyl resveratrol and 3,5,4'-tri-O-hexanoyl resveratrol were then hydrolyzed using lipase (C. …

Drug Design, Biological Activity, And Metabolic Consequences Of Cytotoxic Platinum Compounds: Utilizing Fluorescent Tagging To Understand Drug Action And Metabolism, Brad Benedetti

Theses and Dissertations

Platinum drugs are among the most commonly used chemotherapeutics for the treatment of testicular, head and neck, ovarian, small cell lung, and colorectal carcinomas. Although the current set of platinum chemotherapeutics has proven somewhat successful, the overall success of platinum based drugs is limited due to acquired drug resistance and a limited range of tumor types that are treatable with the current regime. The development of novel cytotoxic platinum based compounds, both trans- and polynuclear, provides for the promising treatment of clinical platinum drug resistant tumors. While the cytotoxic activity of platinum drugs provides for a hopeful outlook, the ultimate …

Synthesis And Analytical Evaluation Of Folate Conjugates For Use In Cancer Cell Detection, Rakeshkumar V. Desai

All Capstone Projects

Folate receptors have two glycosyl phosphatidylinositol anchored isomers, alpha and beta. Folate receptor alpha binds with high affinity for folic acid and act as a receptor for mediated transport of folate into the cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased necessity for folic acid. Folate receptor alpha levels eminent in specific malignant diseases (like solid tumors and leukemia) and thus folate receptors serve in the detection of FR+ (Folate receptor positive) and diagnosis of cancers.

In general, liposomes have the capacity intake the most imaging and toxic …

Analysis Of The Effect Of Various Ligands On The Hydrolysis Of Ruthenium (Iii) Complexes And Interpretation Of Kinetics Of Hydrolysis Profiles By Uv-Visible Spectrophotometry, Sudheer Koneru

Master's Theses and Doctoral Dissertations

Cancer is one of the major causes of death in the world. Discovery of platinum metal-based drugs like cisplatin and carboplatin have proved to be successful in cancer treatment. Due to subsequent development of resistance, side effects, and fewer toxic effects of these drugs, the usage of these drugs has been limited. Novel drugs were being synthesized utilizing the transition metals like ruthenium, osmium, and copper.

In this research, ruthenium metal complexes of the formula HL[RuCl4L2] (where L= ligand) were synthesized. These ruthenium-based drugs exist in prodrug forms which are activated into antitumor drugs by means of hydrolysis, redox reactions, …

Mechanisms Of Cytotoxicity Of Diepoxybutane, Epichlorohydrin And 1-(Chloroethenyl)Oxirane, Rebecca D. Kamins

Honors Theses

Diepoxybutane (DEB), epichlorohydrin (ECH), and 1-(chloroethenyl)oxirane (COX) are small molecules that can form DNA interstrand cross-links. All three of these compounds are, or are metabolites of, industrial chemicals linked to cancer. Additionally, DEB is a metabolite of treosulfan, an anti-cancer drug. We are trying to determine why some of these compounds cause cancer and some can also cure cancer. To do so, we are attempting to link cytotoxicity, cross-linking efficiency, and apoptotic potential of the three compounds to see if any correlations exist. The purpose of this project was to quantify apoptotic potential of DEB, ECH and COX. This was …

Phytochemical Analyses Of Bioactive Compounds In The Roots Of Cassia Alata Linn And The Anti-Angiogenic Evaluation Of Rhein As A Therapeutic Agent Against Breast Cancer Cells, Vivian Esther Fernand

LSU Doctoral Dissertations

The research presented in this dissertation includes the novel phytochemical analysis of root extracts of Cassia alata L. and the anti-angiogenic evaluation of rhein in the treatment of breast cancer. To conduct these studies a combination of analytical techniques were employed, namely, chromatographic, spectroscopic, and bioanalytical. The first part of this research is focused on the phytochemical analysis of C. alata root extracts. A high performance liquid chromatography method was developed and validated for the determination of six phenolic compounds in the root extracts. The investigated compounds were identified by their ultraviolet spectra. Additionally, the presence of these phenolics was …

Inhibition Of The Nf-Kb Signaling Pathway And Its Effects On Apoptosis And Cancer, Joseph A. Lupica

ETD Archive

The Rel/NF-kB family of inducible transcription factors are evolutionarily conserved structurally and functionally, from insects to humans. They are ubiquitously expressed in a number of mature cell types, playing a pivotal role regulating cell growth, differentiation and apoptosis. Under normal circumstances, the proliferation of new cells is tightly regulated, as is the programmed lifespan of most cells, occasionally however cells loose their responsiveness to growth control mechanisms, resulting in a tumor or neoplasm. Sustained or chronic inflammation has been linked to a number of pathological conditions that destroy tissue and facilitate neoplastic growth. NF-kB in part mediates the opposing signals …

Pyridinium Bis-Retinoids A2-Dopamine And A2-Cadaverine: Implications In Age-Related Macular Degeneration And Cancer, Mckenzie Ruth Pew

Theses and Dissertations

Age-related macular degeneration (AMD) is the leading cause of blindness in the United States of America. The pyridinium bis-retinoid A2-ethanolamine (A2E) has been implicated to play a role in AMD. We have observed novel pyridinium bis-retinoids through melanolipofuscin and human RPE extractions that may also play a role in the pathology of AMD. We have begun the construction of an amino-retinoid library in order to identify these ocular compounds. The compounds from the amino-retinoid library are also used in a targeted and triggered drug delivery system for treating cancer. Folic acid is coupled with the amino-retinoids to specifically target cancer …

Synthesis Of Novel Aziridine Derivatives Of Podocarpic Acid, Stephen Rhoden

Electronic Theses and Dissertations

Podocarpic acid (a diterpenoid resin acid extracted from the Podocarpacea specie of plants) has shown cytotoxicity against carcinoma of the nasopharynx. Since this discovery has been made, research has been performed in order to alter the structure of the resin acid so as to increase the anticancer activity. The carboxylic acid and phenol functional groups, which are present in podocarpic acid, make it possible to synthesize new derivatives selectively at the C-15, C-13, and C-7 positions as well as by substitution of the phenol hydroxyl group. Thus numerous derivatives can be prepared, in high yield, for the purpose of investigating …

Mechanisms Of Accumulation And Biological Consequences Of Polynuclear Platinum Compounds, Peyman Kabolizadeh

Theses and Dissertations

The novel trinuclear complex, BBR3464 has undergone Phase II clinical trials and been shown to have greater cytotoxicity and cellular uptake than clinical anticancer platinum drugs such as cisplatin, oxaliplatin and carboplatin. The clinical efficacy of cisplatin, oxaliplatin and carboplatin is limited due to acquired resistance and dose limiting side effects. The three major pharmacological factors contributing to the intrinsic cytotoxicity of, and cellular resistance to, platinum drugs are (i) cellular uptake and efflux of platinum; (ii) the frequency and nature of Pt-DNA adducts; and (iii) deactivating metabolic reactions with sulfur-containing nucleophiles. Since decreased cellular uptake of platinum drugs is …

Cell Toxicity And Uptake Of Rrr-Alpha-Tocopheryl Polyethylene Glycol 1000 Succinate (Tpgs) By Various Cell Ines In Vitro., Christelle Komguem Kamga

Electronic Theses and Dissertations

This research focused on investigating and comparing the cytotoxicity and cellular uptake of RRR-alpha-tocopheryl polyethylene glycol succinate (TPGS, with that of alpha-tocopheryl succinate (α-TS). Both TPGS and α-TS are water-soluble forms of vitamin E with important clinical applications. Cytotoxicity assays with RAW 264.7 and LNCaP cells incubated overnight with TPGS or α-TS at concentrations ≥ 12.4 μM suggest that α-TS is more cytotoxic than TPGS. Macrophages were found to be more sensitive than LNCaP cells when treated with similar concentrations of α-TS. For both cell lines, most of the TPGS or α-TS taken up remained esterified after 24 hours. Our …