Chemicals and Drugs Commons^™

Revision Of Introductory Chemistry Lab Curriculum To Incorporate Inquiry-Based Experiments To Enhance Student Learning, Christian Santos

Honors Program Theses and Projects

The Chemistry Department at BSU is restructuring its curriculum to integrate and scaffold research into the four-year curriculum as part of a CUR-NSF grant. The overall goal of this Honors Thesis was to contribute to the Introductory Chemistry laboratory (CHEM 141L) curriculum development by selecting experiments that move away from traditional “cookbook” laboratory experiments to inquiry-based labs to better engage students and maximize their learning. Three skills identified by chemistry faculty as essential for the restructured CHEM 141L are: preparation of solutions; use of standard curves in quantitative analysis; and graphical analysis of data using Excel. The specific goals of …

Assessing The Effect Of Chronic Dopamine Receptor 2 Blockade As A Potential Model Of Secondary Negative Symptoms In Rats Using The Fr5/Chow Feeding Choice Task, Cyrene Nicholas

Honors Scholar Theses

Haloperidol, a dopamine (DA) D2 receptor antagonist, is an antipsychotic drug which is commonly used to treat schizophrenia and other psychiatric disorders. These disorders are often characterized by elevated striatal dopamine, which is speculated to have a role in producing positive symptoms such as hallucinations, delusions, and paranoia, as well as symptoms related to motivational salience and reward prediction. Individuals with schizophrenia also exhibit negative symptoms, such as amotivation, anergia, fatigue, and apathy among others. While some negative symptoms of schizophrenia are inherent to the pathophysiology, other negative symptoms are hypothesized to be partially induced by chronic exposure to antipsychotic …

Screening And Characterization Of A Pan-Gtpase Inhibitor, Leyla Akhadov

Biomedical Engineering ETDs

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound …

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, …

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 …

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 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% …

Drug Courts And The Following Of The Federal Guidelines, Charles James Souza

Master’s Theses and Projects

During the 1980’s, drug offense were running high within the United States. The court system along with the police and other fields were forced to form other methods of dealing with offenders who have a substance abuse problem. In 1989, the first drug court in the United States was formed in the state if Florida. The idea was to create a therapeutic method to help those who are committing non-violent criminal acts due to their addiction. The goal of drug court was to get offenders the treatment they needed so they would not resort to criminal activity. Drug court personal …

Effects Of Nicotinamide Riboside And Beta-Hydroxybutyrate On C. Elegans Lifespan, Jeffery Peters

Undergraduate Honors Theses

The nicotinamide riboside (NR) form of vitamin B₃and the ketone body ß-hydroxybutyrate (BHB) are two of the most promising natural compounds yet identified for the treatment of aging and aging-related diseases. Forms of vitamin B₃are precursors for the synthesis of the coenzymes nicotinamide adenine dinucleotide (NAD(H)) and nicotinamide adenine dinucleotide phosphate (NADP(H)). In aged cells levels of NAD⁺decline, decreasing metabolism and decreasing activity of protective sirtuin protein deacetylases. In aged cells NR, but not more common forms of vitamin B3, boost NAD⁺levels. BHB is naturally produced by the body when individuals fast …

Hailey-Hailey Disease Successfully Treated With Low-Dose Naltrexone, John Moesch, Richard Miller

West Florida Division GME Research Day 2020

Hailey-Hailey disease (HHD) is an uncommon autosomal dominant disorder resulting from a mutation in the ATP2C1 gene resulting in dysfunction of the Golgi apparatus calcium-associated ATPase, thus interfering with intercellular calcium signaling.

HHD presents clinically as flaccid blisters and erosions in intertriginous areas, especially the axillae and groin.

The major histologic finding is acantholysis throughout the spinous layer of the epidermis, commonly referred to as a “dilapidated brick wall” appearance.

The initial lesions and associated symptoms usually develop during the second or third decade of life.

Complications of HHD include infections (bacterial, fungal, and viral), and malignant transformation (cutaneous squamous …

Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root

Undergraduate Honors Theses

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid …

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the …

Surface-Enhanced Raman Spectroscopy For Cocaine Detection, Kiersten Jo Mead

Chemistry

The detection of drugs of abuse using Raman spectroscopy is of particular interest to forensic researchers at the moment. Raman spectroscopy is highly specific, fast, non-destructive, and can be adapted for in-situ measurements, making it the ideal forensic technique. Researchers working under the guidance of Doctor Igor Lednev have been able to use UV resonance Raman spectroscopy to detect cocaine in oral fluid without the need for sample pretreatment. They were however unable to detect the cocaine at forensically relevant levels. To overcome this limitation, surface-enhanced Raman spectroscopy (SERS) was used in this proof of concept study for the detection …

Impact Of Epa And Dha Supplementation And 15-Lox-1 Expression On Colitis And Colitis-Associated Colorectal Cancer, Jonathan Jaoude

Dissertations and Theses (Open Access)

Inflammatory bowel disease (IBD) patients not only suffer from colitis but also from increased morbidity and mortality of colitis-associated colorectal cancer (CAC). The enzyme 15-lipoxygenase-1 (15-LOX-1) is crucial to converting omega-3 fatty acid derivatives eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to resolvins, potent anti-inflammatory products. 15-LOX-1 effects on the conversion of EPA and DHA to resolvins that subsequently exert anti-inflammatory and anti-tumorigenic effects have received little attention. To address this knowledge gap, we hypothesize that 15-LOX-1 expression in colonic epithelial cells is essential for resolvin biosynthesis from EPA and DHA to modulate immunophenotype, limit inflammation, promote resolution, and help …