Chemicals and Drugs Commons^™

Variability In Naltrexone Biotransformation, Stephani L. Stancil

Research Days

No abstract provided.

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

Selective Autophagy Maintains The Aryl Hydrocarbon Receptor Levels In Hela Cells: A Mechanism That Is Dependent On The P23 Co-Chaperone, Yujie Yang, William K. Chan

School of Pharmacy Faculty Articles

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation …

Disruption Of The Electron Transfer System Within The Protein 3-Ketosteroid-9Α-Hydroxylase (Kshab) Of Mycobacterium Tuberculosis, Olivia Esteireiro

Honors Program Theses and Projects

Uncovering the mode of electron transport within the 3-ketosteroid-9-hydroxylase, KshAB, enzyme complex from Mycobacterium tuberculosis will reveal previously unknown possibilities towards curing tuberculosis infections. The KshB protein was mutated at one possible site of electron transfer – an arginine at location 286 – to rupture its cooperation with the KshA complex to prevent the bacteria from gaining energy from the breakdown of steroids as a fuel source. The arginine was mutated to an aspartic acid and alanine to get varying chemical properties to replace the original amino acid. Experimentation included over-expressing the wildtype and mutant proteins in E. coli, …

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Synthesis Of Aromatic Fluorinated Ketones For Evaluation At The Gaba Receptor, Madeline Griffin

Honors Theses

GABA is a neurotransmitter that inhibits the excitation of neurons. Targeting this specific receptor has the potential to inhibit the central nervous system and possibly treat addiction, anxiety, or mood disorders. Previous research has shown that fluorinated ketones can have valuable applications in the medicinal chemistry of addiction. Some fluorinated ketones have shown activity at the GABA receptor. The main goal of this project was to synthesize aromatic fluorinated ketones for biological evaluation at the GABA_B receptor. Another goal was to compare both the monofluorinated and difluorinated analogues synthesized in order to quantify differences in activity from fluorination state. …

A Raman Spectroscopic And Quantum Chemical Investigation Of Serotonin, It's Intramolecular Interactions, And The Solvent Effects Of Methanol, Ethanol, And Water, Mallory Loe

Honors Theses

Serotonin, or 5-hydroxytryptamine, is a neurotransmitter and metabolite vital to the normal function of the cardiovascular, gastrointestinal, and nervous systems. Although it might be colloquially known as the ‘happiness drug,’ malfunctions in serotoninergic pathways can result in mental health disorders, heart disease, irritable bowel syndrome, and even collateral death. Without a current method to directly measure, or even detect, serotonin in the human body, these diseases, along with many others, pose a threat of developing without proper warning. Raman spectroscopy presents a unique method to vibrationally characterize molecules based upon the inelastic scattering of light. Serotonin’s unique, amphipathic structure presents …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Synthesis And Characterization Of Pamam-Fatty Acid “Janus-Type” Dendritic Hybrids For Biomedical Applications, Abigail Grace Barker

Honors Theses

Janus dendrimers are amphiphilic macromolecules that have shown promising potential in the biomedical field. Due to their unique structure and properties, these branched block copolymers have the ability to self-assemble into bioinspired spherical nanoaggregates. Because they possess a hydrophobic and hydrophilic moiety, these aggregates show potential as drug delivery systems that can transport both hydrophobic and hydrophilic drugs. However, many of the proposed dendrimer systems suffer from certain weaknesses that hinder their practical usage as clinical treatment options. Some of these shortcomings include specificity, solubility, size, surface charge, and mechanical properties. To combat these problems, we synthesized and characterized a …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

The Histone Deacetylase Inhibitor Largazole: A Potential Chemotherapeutic Agent, Hannah Lynn Carson

Honors Theses

Histone deacetylase enzymes are known for their inherent activity as epigenetic modifiers. Although, they have become recognized for their role in cancer progression and other diseases. But also, histone deacetylases have other non-histone targets, for example, microtubules, which play important roles in cancer metastasis, apoptosis, and replication. With histone deacetylase inhibitors (HDACi), our research explored HDACi effects on breast cancer cell lines. The overall goal was to understand the potential of largazole, a class one histone deacetylase inhibitor on breast cancer cell lines. The research consisted of two parts: sulforhodamine B (SRB) viability assays under hypoxic and normoxic conditions. The …

Study Of Pharmaceutical Tablets Using Raman Mapping, Kyle Joseph Pauly

Honors Theses

Covalent bonds are the strongest type of bonds holding molecules together. Based on the pattern of bonding of the molecule, the atoms associated with the bond will vibrate at a specific frequency. Utilizing vibrational spectroscopy, such as Raman spectroscopy, these unique vibrational frequencies can be used to detect the presence of analytes over a selected area. Furthermore, the intensities of the vibrational modes can be tracked to comparatively quantify the concentration of analytes at various locations. This is a method of great importance due to its ability to compare pharmaceutical tablets synthesized with different techniques. Here, the presence and concentration …

Detection And Characterization Of Delta-9-Tetrahydrocannabinol And Novel Synthetic Cannabinoid Metabolites Using Human Liver Microsomes, Seema Murugan

Honors Theses

Marijuana and synthetic cannabinoids are the most commonly used and trafficked illicit drug. ∆⁹-tetrahydrocannabinol (THC) is the primary active compound in marijuana. Synthetic cannabinoids were created as a method to study the effects of cannabinoids on the endocannabinoid system, which consists of endogenous cannabinoids, cannabinoid receptors, and the synthetic and degrading enzymes responsible for the synthesis and degradation of endocannabinoids. Cannabinoids activate the same receptors as endocannabinoids. Synthetic cannabinoids gained popularity as recreational drugs due to their ability to avoid detection. Synthetic cannabinoids have been found to have a greater binding affinity to the cannabinoid CB₁ receptor …

Synthesis Of Pharmaceutical And Personal Care Products And Pesticide Metabolites Of Environmental Concern, Isaiah Edwards

Honors Theses

Human pollution of aquatic environments by introduction of pharmaceutical and personal care products (PPCPs) as well as agrichemicals presents a grave threat to the health of aquatic organisms. Many of these chemicals not only exhibit toxicity to the species of complex ecosystems at various levels but also undergo metabolic transformation into moieties that have different and sometimes more potent physiochemical profiles. PPCP and pesticides as well as their metabolites impact organisms via a number of different mechanisms, with the most serious arguably being endocrine disruption. Two emerging pollutants, gemfibrozil and bifenthrin, possess naturally occurring metabolites that were determined to warrant …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Using A Novel Cell- Penetrating Peptide Technology To Induce Pluripotency, Laura-Maria Oja

Master of Science in Chemical Sciences Theses

Somatic stem cells have been used as a regenerative medicine tool to treat diseases like leukemia for decades, but they are limited in their ability to self-renew and differentiate. A better alternative, induced pluripotent stem cells (iPSCs), has the ability to generate cells from all three germ layers and avoid tissue rejection as well as bypass the ethical concerns related to embryonic stem cells. In 2006, Takahashi and Yamanaka discovered that only four genes were required to induce pluripotency: Oct4, Sox2, Klf4, and c-Myc (OSKM). Since then, pluripotency has been induced with OSKM most effectively by transfection or transduction. However, …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …