Digital Commons Network^™

Synthesis Of New Platinum-Based Anti-Cancer Drugs, Saud O. Albaroodi Yasser

Masters Theses

Cancer is considered the second leading cause of death after heart attack. Different treatments have been applied to kill cancer cells such as chemotherapy, which is the use of chemicals or drugs in order to treat cancer cells. Platinum-based anti cancer drugs are the backbone of chemotherapy, they play a crucial role in treating various malignant tumor. However, the disadvantages of these drugs are very painful on patients, such as nephrotoxicity and ototoxicity. In the last four decades, thousands of platinum-based anticancer drugs have been synthesized for hope in find a new drug with higher efficacy and less side effects.In …

Biochemical And Structural Characterization Of The Core Subunits Of Gpi Transamidase, Dilani G. Gamage

Wayne State University Dissertations

BIOCHEMICAL AND STRUCTURAL CHARACTERIZATION OF THE CORE SUBUNITS OF GPI TRANSAMIDASE

by

DILANI G GAMAGE

May 2015

Advisor: Prof. Tamara L. Hendrickson

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

Glycosylphosphatidylinositol transamidase (GPI-T) is a complicated, membrane-bound, multi-subunit enzyme that catalyzes an essential post-translational modification. This enzyme attaches GPI anchors to the C-termini of various proteins that contain a proper GPI-T signal sequence. Gpi8, Gaa1, Gpi16, Gpi17 and Gab1 are the five known subunits that may encompass the fungal GPI-T; Gpi8 is the catalytic subunit, but the functions of the other subunits remain essentially unknown. In humans, different GPI-T subunits are …

Biological Evaluation Of The Vaccine Candidate Tf-Ps A1 And A One-Pot Multicomponent Coupling/Cyclization For Natural Product Herbicide (±)-Thaxtomin A, Jean Paul Bourgault

Wayne State University Dissertations

ABSTRACT

BIOLOGICAL EVALUATION OF THE VACCINE CANDIDATE TF-PS A1 AND A ONE-POT MULTICOMPONENT COUPLING/CYCLIZATION FOR NATURAL PRODUCT HERBICIDE (±)-THAXTOMIN A

By

JEAN PAUL BOURGAULT

August 2015

Advisor: Prof. Peter R. Andreana

Major: Chemistry (Organic)

Degree: Doctor of Philosophy

The -aminooxy derivative of the Thomsen–Friedenreich tumor associated carbohydrate antigen has been synthesized in 11 steps utilizing a D-GalN3 acceptor carrying a pre-installed -N-hydroxysuccinimidyl moiety. The natural  linkage was prepared in high selectivity employing a suitably protected D-GalN3-thioglycoside donor with N-hydroxysuccinimide. With access to -TF-ONH2, the preparation of the TF-PS A1 vaccine candidate ensued smoothly through oxime bond formation. This construct …

Synthesis, Surface Functionalization, And Biological Testing Of Iron Oxide Nanoparticles For Development As A Cancer Therapeutic, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles are highly researched for their use in biomedical applications such as drug delivery, diagnosis, and therapy. The inherent biodegradable and biocompatible nanoparticle properties make them highly advantageous in nanomedicine. The magnetic properties of iron oxide nanoparticles make them promising candidates for magnetic fluid hyperthermia applications. Designing an efficient iron oxide nanoparticle for hyperthermia requires synthetic, surface functionalization, stability, and biological investigations. This research focused on the following three areas: optimizing synthesis conditions for maximum radiofrequency induced magnetic hyperthermia, designing a simple and modifiable surface functionalization method for specific or broad biological stability, and in vitro and in …

Light Controlled Drug Activation And Release, Jonathon Sheldon

Theses and Dissertations

Cancer constitutes a terrible burden on modern society. In the United States there are an estimated 1,658,370 new cancer diagnoses resulting in 589,430 deaths in 2015 alone.^[1] An estimated 41,170 of these cases will be diagnosed right here in Virginia. With new cancer patients comes the expanding demand for new treatments. As we all know, many modern chemotherapeutics cause adverse reactions to patients. This is because the toxic nature of these therapies often affects normal tissue alongside the tumors that are infesting the body. Therefore, researching novel ways to make chemotherapeutics selective for cancer, while leaving healthy tissue unscathed, …

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C² substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by ¹H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. …

Synthesis And Anti-Proliferative Activity Of N,N’-Bis(Arylmethyl)Benzimidazolium Salts, Travis M. Williams

Williams Honors College, Honors Research Projects

A series of N,N’-bis(arylmethyl)benzimidazolium salts with hydrophilic and lipophilic substituents have been synthesized, characterized, and tested against select non-small cell cancer cell lines. Substituent variations on the imidazole ring have shown that lipophilicity and hydrophilicity can influence the imidazolium salts’ anti-proliferative activity and aqueous solubility.