Pharmacy and Pharmaceutical Sciences Commons^™

Analyzing Functional Interactions Of Designed Peptides By Nmr Spectroscopy, Wonsuk Choi

Pharmaceutical Sciences (MS) Theses

The development of small peptide-based therapeutics can be accelerated by the knowledge of relationships between the peptide structure and its functional interactions. Here, we report the analysis of two groups of synthetic peptides designed for two applications – broad bactericidal action and inhibition of protein-protein interactions in human cells. Novel amphiphilic peptides designed for antibacterial application incorporated arginine as cationic amino acids and non-natural amino acids that have aromatic side chains with similar hydrophobic properties as tryptophan. The interaction of lead cyclic peptides and their linear analogs with a phospholipid bilayer mimicking a bacterial membrane was studied using nuclear magnetic …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

Computer-Aided Drug Design Of Bakuchiol-Inspired Lxrα Modulators Against Acute Lymphoblastic Leukemia, Dillon P. Cao

LSU Master's Theses

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children, accounting for approximately 25% of pediatric malignancies. Although glucocorticoids are commonly used to treat ALL, prolonged use can lead to steroid resistance, rendering the drug regimen ineffective. Therefore, alternative treatment avenues are needed for high- risk pediatric patients that do not respond well to traditional regimens.

Liver X Receptor α (LXRα) is presented as a potential alternative drug target for pediatric patients that exhibit suboptimal response to glucocorticoids. Limitations of the current LXRα modulators such as indiscriminate isoform selectivity between LXRα and LXRβ and consequent adverse effects …

The Opioid Epidemic: How Genetics Play A Role In Addiction And Treatment, Kirsten Houston

Honors College Theses

The opioid epidemic is an issue within the pharmaceutical industry in the United States of America due to prescription and non-prescription substances being made available to the population. Opioids include chemical substances that affect the body and brain through opioid receptors, including the mu, kappa, and delta receptors. These substances are derived and synthesized from the poppy plant. Multiple causes have been linked to opioid abuse disorder, including but not limited to employment, income, housing, nutrition, mental health disorders, and genetics. By gathering information from previous literature, genetics may be the main cause of narcotic analgesic tolerance and abuse. Specific …

All Clear: A Workbook For Sexually Active Accutane Users Who Can Become Pregnant, Taylor Petersen

Honors Projects

Accutane is a pill-based derivative of Vitamin A used to treat cystic acne. The process to start and continue the medication each month is tedious and full of potential for error. This is especially true for female patients who are able to become pregnant as they have the additional step of monitoring and updating their birth control through an online portal. Patients are treated like numbers and there is little to no customization within Accutane treatment from patient to patient. To make this worse, reliable information about the drug is scarce and many turn to social media platforms or other …

Genetic Mutations Of KCa2.3 And KCa3.1 Channels Affect Ca2+ Sensitivity, Razan Orfali

Pharmaceutical Sciences (PhD) Dissertations

The Ca²⁺-activated potassium channels K_Ca channels are a unique family of potassium channels activated by intracellular calcium. K_Ca channels are critical for maintaining K⁺ homeostasis and modulate several physiological processes, from the firing properties of neurons to the control of the transmitter release. The Ca²⁺ sensitivity of these channels allows intracellular Ca²⁺ to regulate the electrical activity of the cell membrane. Increased Ca²⁺ sensitivity of K_Ca channels caused by gain of function mutations (GOF) in the KCNN genes results in a broad spectrum of human channelopathies, including Zimmermann- Laband syndrome (ZLS), …

Self-Assembled Ternary Polypeptide Nanoparticles With Improved Biostability For Drug Delivery In Cancer Therapy, Preye Mike Agbana

Theses and Dissertations--Pharmacy

Cancer remains a real and present threat to global health. In the United States, according to cancer statistics, almost 40% of people will be diagnosed with cancer at some point in their lifetime. Conventional chemotherapy has become the mainstay for cancer treatment option. However, chemotherapeutic agents are plagued with problems such as poor aqueous solubility, chemical degradation, Bio instability, and off-site toxicity due to non-specificity. New drug modalities are needed to tackle the ever-growing burden on cancer. In recent times, the promise of nanotechnology has aided to develop drug delivery vehicles to facilitate the administration of potent chemotherapeutics. Nanoformulations such …

Right Treatment Wrong Time: Immunotherapy Administration Post-Radiotherapy Decreases Tumor Burden In A Preclinical Model Of Brain Metastasis, Kathryn Elizabeth Blethen

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in-depth literature review of methods to modulate the blood-brain and blood-tumor barriers to increase drug delivery and efficacy in brain metastases, (b) evaluated the effects of whole-brain radiation therapy on the blood-brain barrier in immunocompetent and immunocompromised mouse models and proposed a mechanism by which the immune response to radiation disrupts the blood-brain barrier, and (c) developed a syngeneic lung cancer brain metastasis model to determine the impact of coordinated immunotherapy administration with radiotherapy. The blood-brain barrier is an impediment to drug delivery to the brain. The inherent leakiness of the blood-tumor barrier does not …

Physiologically-Based Pharmacokinetic (Pbpk) Modeling For The Preclinical Development Of Spectinamide Antibiotics, Keyur R. Parmar

Theses and Dissertations (ETD)

Despite being an ancient disease caused by Mycobacterium tuberculosis (Mtb) and after decades of research, tuberculosis (TB) still affects millions of people every year worldwide. In 2018, the World Health Organization (WHO) reported that 10 million people developed tuberculosis and 1.5 million died of the disease. With the increase in the multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, the treatment for TB with the standard first and second-line therapy is becoming increasingly difficult. Therefore, there is an urgent need to find new anti-TB drugs as combination partners of existing and experimental classes of antimicrobial agents to shorten and simplify the …

Pharmacology Of Disulfiram As An Antibacterial Agent, Yogesh Meka

Theses, Dissertations and Capstones

Disulfiram (Antabuse®) is an oral prescription drug used to treat alcohol abuse disorder (AUD). Disulfiram (DSF) and its metabolites act on the body by inhibiting multiple enzymes involved in alcohol metabolism. This study aims to understand the pharmacology of disulfiram as an antibacterial medication. Previous studies on DSF showed antibiotic activity against multidrug-resistant Staphylococcus aureus strains (MRSA). The initial aim of this study was to decipher the mechanisms involved in inhibiting bacterial growth by DSF, which was done by performing biochemical studies. The studies revealed that DSF had antagonistic effects on redox buffering and energy production. Another aim of this …

Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic

Theses and Dissertations--Pharmacy

Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …

Cultivating Health, Not Wealth In The United States' Healthcare System: Comprehensive Revisions For The Orphan Drug Act Of 1983, Kayla Smith

Regis University Student Publications (comprehensive collection)

This thesis explores the way in which the Orphan Drug Act of 1983, originally instituted in response to a lack of treatments for rare diseases in the United States of America, has failed to achieve its initial objectives in the 40 years since its implementation. In evaluating various successful examples of government subsidization programs designed to intervene in private industry, this thesis composes the criterion required for funding-based legislation which maximize market outcomes while minimizing tax-payer burden. An analysis of the synthetic organic chemistry industry – and a case study into the production of a particular orphan treatment for a …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Assessing Drug Development Proporties Of Antithrombotic And Anti - Cancer Agents, Elsamani I. Abdelfadiel

Theses and Dissertations

The current GAG anticoagulants such as heparin, heparin derivatives, and vitamin K antagonists, such as warfarin continue to be the backbone of anticoagulant therapy. These drugs act through an indirect mechanism to convey inhibition of several coagulation enzymes. However, xv their use leads to several serious adverse effects, such as excessive bleeding risk and unpredictability of patient response. Regardless of their clinical achievement, every individual agent is accompanied by several side effects, particularly major/minor bleeding, thrombocytopenia, drug-food or drug-drug interactions, or absence of antidote. Of all these side effects, bleeding, and a lack of an effective antidote to reverse excessive …