Chemistry Commons^™

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, …

Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey

Masters Theses & Specialist Projects

Platinum(II) anticancer medications essentially react with DNA forming kinks in
the double helix of DNA and causing apoptosis. It has also been noted that these
anticancer medications react with methionine and cysteine in the body. With the new discoveries of selenium containing amino acids including selenomethionine and selenocysteine, new research is ongoing to see what types of products can be formed from these amino acids. Our research reacts [Pt(Met-S,N)Cl₂] ²⁺ with selenomethionine to determine what types of products are produced. Monochelates including [Pt(SeMet-Se,N)Cl₂] ²⁺ have formed two isomers, …

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 …

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 …

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 …

Solar Synthesis Of Acyl Hydroquinones And Their Bioactivity., Fernando De Leon, Shizue Mito

COURI Symposium Abstracts, Summer 2012

Without the Sun, we would not enjoy the benefits of life here on the Earth. This energy is essential and crucial for sustaining life: playing important roles in circadian rhythms and photosynthesis in plants. In our research, this endlessly renewable clean energy source is utilized for photo-Friedel-Crafts acylation of 1,4 - benzoquinones and 1,4 - naphthoquinones. Photo-Friedel-Crafts acylation was first discovered in 1891 and although there have been reported examples of acylated products, the substrates are still limited. In this project a variety of aldehydes having different substituents are examined, and bioassays were performed. While conventional methods for photochemistry use …

Development Of Novel Non-Invasive Diagnostic Methods For Early Detection Of Prostate And Breast Cancer, Marisol Sanchez^, Olivia C. Jones, Wen-Yee Lee*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

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 …

Progress Towards A Facile Synthesis Of A Gadolinium (Iii) Octabrominated Porphyrin, Tseng Xiong

The Corinthian

Towards preparing porphyrin complexes that combine contrast agent and photodynamic therapy capabilities at tumor sites, the Gd(III) porphyrin derivative of the octabrominated meso-tetrakis(N-methyl-4-pyridyl)porphyrin, GdTMPyPBr8 5+ was synthesized by refluxing Gd(III) ion with H3TMPyPBr8 5+ at pH 7. The metallocomplex was characterized by UV-visible spectroscopy and showed a Soret band shift from 503 nm to 463 nm at pH 7, suggesting that metal insertion of Gd(III) into the core of porphyrin ligand had occurred. However, synthesis of the Gd(III) complex required high temperatures and long reaction times. To circumvent these harsh conditions, the lithium porphyrin derivative was first prepared and subsequently …

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 …

Orally Active Mmp-1 Sparing Α-Tetrahydropyranyl And Α-Piperidinyl Sulfone Matrix Metalloproteinase (Mmp) Inhibitors With Efficacy In Cancer, Arthritis, And Cardiovascular Disease, Daniel P. Becker, Thomas E. Barta, Louis J. Bedell, Terri L. Boehm

Chemistry: Faculty Publications and Other Works

α-Sulfone-α-piperidine and α-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP’s-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. α-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while α-piperidine and α-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.

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, …

Light-Regulated Sampling Of Protein Kinase Activity (Ii), Collaborative Project

Dyson College- Seidenberg School of CSIS : Collaborative Projects and Presentations

This entry adheres to the use of the quad chart template to provide a succinct description only of the current research project undertaken by the participants. It provides for the following information

1. Participants and Affiliations
2. Overall Project Goals
3. Illustrative picture
4. Specific research/artistic/pedagogic foci

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 …

Microwave Reflectometry As A Novel Diagnostic Tool For Detection Of Skin Cancers, Pratik Mehta, Kundan Chand, Deepak Narayanswamy, Daryl G. Beetner, R. Zoughi, William V. Stoecker

Electrical and Computer Engineering Faculty Research & Creative Works

More than 1 000 000 people are diagnosed with skin cancer each year in the United States, and more than 10 000 people die from the disease. Methods such as visual inspection and dermoscopy are available for early detection of skin cancers, but improvement in accuracy is needed. This paper investigates the use of microwave reflectometry as a potential diagnostic tool for detection of skin cancers. Open-ended coaxial probes were used to measure microwave properties of skin. The influences of measurement parameters such as probe application pressure, power level, and variation in reflection properties of skin with location and hydration …

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 …

An Addictive Cycle Of Chemical Dependence: Pesticides And The Link To Breast Cancer, Misty Sanford

Whittier Scholars Program

This year, an estimated 40,800 women in the United states will die of breast cancer and another 182,800 will be diagnosed with the disease. Breast cancer is the second leading cause of death among women, exceeded only by lung cancer. As the result of earlier detection and improved treatment, death rates among young women have declined since 1992. Yet, at the same time, the incidence of breast cancer in American women has increased by a startling forty-four percent. The most pressing question is: what is causing this increase? Established risk factors include a family history of breast cancer , early …