Chemicals and Drugs Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

A Study Of The Antioxidant Versus Pro-Oxidant Nature Of The Amyloid Beta Peptide And An Analysis Of The Natural Products, Isorhamnetin And Narignenin, As Antioxidants, Kaylee Holmes

Honors Theses

Alzheimer’s disease is a neurodegenerative disorder with no cure. Due to the widespread effects of this disease, abundant research efforts have gone towards finding a cure. The amyloid beta (Ab) peptide has been shown to be a potential cause of the disease due to destructive effects on tissues that it can have both by itself and through reactive oxygen species (ROS) generation. This study was performed in order to assess the structural properties of Ab₄₂monomers, fibrils and oligomers, to assess the antioxidant versus pro-oxidant behavior of the Ab peptide, and to assess the antioxidant nature of the natural …

Diabetes Debunked: What You Need To Know, Maggie Hutson

Honors Theses

The goal of this Honors creative project is to encourage health literacy in populations who are curious about Type 2 Diabetes or have Type 2 Diabetes. From personal experience, I have seen noncompliance in diabetics and wondered why since it is a serious, progressive disease. After researching, I found that some diabetics do not understand the scope of their disease, especially since many of the dangerous complications that arise from Type 2 Diabetes do not present until later in the disease when it is too late. For my senior project, I decided to write an educational paper as a supplement …

Pharmaceutical Manufacturing In The 21st Century: Identification And Analysis Of Key Elements, Robert N. Mills

Honors Theses

The availability of quality pharmaceutical products impacts the lives of the global population on a daily basis. The importance of product availability and quality within pharmaceutical manufacturing requires that quality systems put into place are capable of accurately and robustly capturing the quality compliance, or lack thereof, of the various stages of production. This review intends to analyze current expert-recommended best practices within key elements of a pharmaceutical manufacturing quality control system and provide recommendations throughout. The quality elements discussed include Quality by Design method validation, necessary equipment determination, and equipment qualification, followed by documentation control and data flow.

Determining The Presence Of Bpa In Vaping Mouthpieces, Jessica Cook-Snelgrove

Honors Theses

As more and more teenagers and young adults begin to vape, whether it be to quit smoking or to look cool, there is a potential for them to be exposed to bisphenol-A (BPA) through the plastic mouthpieces on the vapes. BPA is a molecule that is added in many plastics to make the plastic harder (Houlihan, Lunder, & Jacob, 2008). Unfortunately, BPA is structurally similar to estrogen as can be seen in Figure 1. The closeness of the structures can cause issues in humans such as cardiovascular disease, diabetes, and reproductive problems (Houlihan, Lunder, & Jacob, 2008). In recent years, …

Development Of A Chemical Genetic Screen To Identify Compounds That Enhance Laromustine Cytotoxicity, Xiaoou Wang

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials against acute myeloid leukemia. Though laromustine showed some success in clinical trials, more experiments are needed to understand the hematological toxicity and the molecular mechanisms of patients’ resistance. This project aims to develop a strategy to identify compounds synergistic with laromustine in cultured leukemia cells from a library of 450 FDA-approved compounds through a forward chemical genetic screen. To optimize the screen, the cell seeding density, doubling time, and dose response curves were determined. The optimized concentration of HL60 cells in these experiments was determined to be between 25,000 and …

Impact Of Single Nucleotide Polymorphisms On Hpa Axis Functionality In Depression, Claire Kelly

Honors Theses

The hypothalamic-pituitary-adrenal (HPA) axis plays a primary role in stress response through the regulated secretion of the glucocorticoid hormone cortisol. Diseases of cortisol dysregulation such as Cushing’s syndrome (hypercortisolemia) and Addison’s Disease (hypocortisolemia) are both associated with depression. Based on this we, and others, have hypothesized that mutations in the genes for the glucocorticoid receptor (GR), the closely related mineralocorticoid receptor (MR), and regulatory proteins associated with cortisol or GR function may contribute to depression in the absence of hyper- or hypo-cortisolemia. Our study investigated the genotypic frequency in the clinical population of several single nucleotide polymorphisms (SNPs) that affect …

Jwh-018 And Selective Serotonin Reuptake Inhibitors: Drug-Drug Interactions And Implications On Toxicity, Christopher O. Godwin

Honors Theses

Drug abuse has expanded from more well-known substances, such as cocaine and marijuana, to relatively new novel psychoactive substances. A group of these substances called synthetic cannabinoids have been increasing in usage throughout the 2000's, and these compounds carry significant and varying risks depending on the dose and composition of the synthetic cannabinoid. Patients have been observed having symptoms associated with high doses of synthetic cannabinoids when they take lower doses of the synthetic cannabinoid in addition to their antidepressant medication. In order to test the effects of co-administration of selective serotonin reuptake inhibitors (SSRis) and synthetic cannabinoids, mice were …

Recombinant Expression And Purification Of Amyloid-Β In E. Coli, Wisam M. Beauti

Honors Theses

Alzheimer’s disease (AD) is a common neurodegenerative disorder that affects people older than 65 years 1,2,5. It is characterized by the presence of extracellular plaque deposits that are seen specifically in the brains of AD patients 4,5. These plaques are mainly comprised of amyloid-β (Aβ) peptide aggregates. Aβ plaque production and deposition is believed to drive AD pathogenesis. Studying these proteins is crucial to understanding aspects of AD in order to develop possible therapeutic treatments. Recombinant expression of Aβ can also provide a handle to introduce mutations in the protein to further study their structure-function relationships. However, synthetic Aβ monomer …

Chitosan Nanoparticle Modifications For Improved Gene Delivery In An Oral Dna Vaccine Application, Austin Helmink

Honors Theses

Vaccines represent one of the most significant medical innovations of the 20^th century, resulting in the eradication or near eradication of a handful of deadly diseases. However, many infectious diseases remain resistant to effective vaccination, largely due to a lack full immune activation by traditional protein-based vaccines. A promising alternative vaccination strategy is the emerging development of DNA vaccines, which rely upon the delivery of exogenous genetic material to host cells encoding for a viral or bacterial antigen in order to induce a robust immune response by closely mimicking live infection. The delivery of genetic material requires a carrier …

Union College Smokers: Hurting Themselves But Helping Others? Mixed Research On The Relationship Between Smoking And Volunteering, Cameron Robertson

Honors Theses

This mixed methodology research project analyzes the relationship between smoking cigarettes and volunteer participation rates utilizing an empirical analysis of 2006 and 2010 Current Population Surveys (CPS), as well as a qualitative analysis on the perception and behaviors of Union College student smokers. Existing studies have indicated a negative association between smoking cigarettes and social participation, yet little research has been done on the specific relationship between smoking status and volunteer participation. Utilizing CPS supplements on tobacco use and volunteering, this empirical analysis finds that smoking cigarettes has a significant association with decreased volunteer participation rates. This research also includes …

Behavioral Sensitization Following Concurrent Exposure To 4-Methylmethcathinone (4-Mmc) And 3,4-Methylenedioxymethamphetamine (Mdma) In Male Sprague-Dawley Rats, Trent Bullock

Honors Theses

Recreational use of a new class of stimulant drugs known as synthetic cathinones is a recent public health concern. Although the Drug Enforcement Administration placed several of the most common of these substances permanently on schedule 1, their use is still prevalent as they remain low cost, accessible, and potent. Concomitant use of cathinone derivatives with other psychostimulant drugs is commonly reported by recreational users. Despite the prevalence of synthetic cathinone abuse, there is currently a paucity of scientific research regarding the behavioral and neurochemical effects of these drugs in mixtures with other drugs of abuse. The behavioral sensitization paradigm …

The Effects Of Aging And Estrogen Treatment During Aging On The Rat Epididymis, Kathryn Davis

Honors Theses

Previous studies from our lab have demonstrated that a normal estrogen environment in the testis contributes to maintaining spermatogenesis in adult rats and that estrogen treatment can attenuate the age-associated decline in sperm production. The purpose of this study was to determine if the estrogen environment of the epididymis is altered with age and what effects estrogen treatment may have on the epididymis during aging. The study compared untreated rats at 15 months of age to 18 month old rats that were treated with either vehicle, or estradiol- valerate, once every third day from 15 to 18 months. Mean concentrations …

Analysis Of Mammalian Carboxypeptidase O Expression Patterns, Christian Bardan

Honors Theses

Carboxypeptidase 0 (CPO) is a protease that cuts acidic amino acids from the carboxy termini of substrate proteins. This study aims to describe the expression patterns of CPO in small mammals. We have sampled tissue from four different species: thirteen-lined ground squirrel, eastern chipmunk, eastern mole, and northern short-tailed shrew. Samples were analyzed via Western blot using two CPO antibodies. Immunoreactive bands likely to be CPO, with molecular weights approximately 42 kDa, were seen predominantly in kidney, liver, and intestinal tissue samples. This suggests CPO could play a specific physiological function in these organs.

The Effects Of Omega-3 Fatty Acids On Intracellular Inositol Levels In Saccharomyces Cerevisiae, Jee Yeon (Joanne) Lee

Honors Theses

Bipolar disorder is a severe and chronic debilitating mental disorder characterized by extreme mood swings between mania and depression. The current medications for bipolar disorder, lithium and valproate, have been associated with numerous negative side effects. Although the therapeutic mechanism by which lithium and valproate (VPA) exert their effect is unknown, a leading hypothesis implicates inositol depletion as a mechanism of action. On the other hand, omega-3-fatty acids have been shown to relieve symptoms of bipolar disorder. In this study, we compare the effects of VPA to the effects of decosahexaenoic acid (DHA) on Saccharomyces cerevisiae growth and intracellular inositol …

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …

Investigating The Impact Of Marijuana Legalization On Income, Education, And Depression, Wayne Fu

Honors Theses

Over the past two decades, marijuana has been the most widely used illicit drug by adolescents in the US. The drug continues to soar in popularity as both a recreational and medicinal drug despite mounting scientific research that marijuana consumption may impair cognitive function including deficits in learning, memory, motivation, and attention. Marijuana use has also been linked to exacerbation of depression and anxiety symptoms. Though federal laws still classify marijuana as an illegal substance, recent state-level legislation has sparked national debate over its legal status. In fact, 23 states and the District of Columbia have legalized marijuana for medical …

Psychostimulant Use Among Undiagnosed College Students: Revealing Perceptions Anddebunking The Myth Of Cognitive Benefits, Rebecca Elizabeth Shait

Honors Theses

Previous research suggests there is a rising trend of non-medical psychostimulant use on college campuses. The current study examined the prevalence of non-medical psychostimulant use, assessed students’ motivations and perceptions of the cognitive and emotional benefits, and attempted to influence their views by giving them real scenarios where psychostimulants are not effective for individuals without ADHD. Results revealed that there is a prevalence of non-medical psychostimulant use at Union College. Non-medical psychostimulant users had a more positive perception that these medications enhance performance, cognition, memory, mood/energy, and motivation to start and complete work. There were no significant interactions or differences …

The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady

Honors Theses

Information available for woman prescribed Adderall to treat ADHD and the effects that it may have on her fetus is limited. However, Adderall and methamphetamine have similar pharmacological and addictive qualities. This paper is concerned with whether there is an adequate approach to treatment that balances the needs of the mother and the fetus. With Adderall use becoming more prevalent, it is essential that society is aware of the physiology and pharmacology of this drug, as well as, the need for more research on this subject to be produced.

The Effect Of Cannabinoids On Triple Negative Breast Cancer Cells, Haley Dahl

Honors Theses

Triple Negative Breast Cancer (TNBC) is a difficult type of cancer to treat because it is negative for progesterone, estrogen, and HER-2 receptors. Because TNBC is negative for these three receptors, it does not respond to normal hormonal therapies. The purpose of my experiment is to see if different cannabinoids, compounds from the cannabis plants, could be used as alternative treatment options. These experiments employed three different cannabinoids: ajulemic acid, cannabidiol, and hemp oil. Cell viability was measured after 72 hours of treatment using a MTT assay. The results showed that the three cannabinoids could be used to effectively destroy …

Thrilling Monotony: A Summer Of Alzheimer's Research, Baronger Dowell Bieger

Honors Theses

The primary genetic risk determinant for late-onset Alzheimer's disease is the apolipoprotein E gene (APOE). Variations in this gene produce three different isoforms of the apolipoprotein E protein (ApoE): ApoE2, ApoE3, and ApoE4. ApoE# is the most common isoform, so rates of LOAD among other genotypes are indexed to this variant. ApoE2 is rather rare, but its carriers are less likely to get LOAD; when they do, they get it later. The second most common variant is ApoE4, and its carriers are significantly more likely to get LOAD. They also tend to succumb earlier. Once developed, LOAD is characterized by …

Ten Weeks With Green Beans...And Then Some: Determination Of Bisphenol-A (Bpa) In Canned Goods From Arkansas Markets Using Fluorescence Spectrophotometry, Rachel Pruett

Honors Theses

Bisphenol A (BPA) is a chemical widely used in production of consumer goods. It has come under scrutiny recently after being labeled as an endocrine disruptor (ED), mostly causing adverse effects in infants and young children. It has been associated with diabetes, cardiovascular disease, and abnormal maturation. Because it is so commonly used in product development, humans are exposed to BPA through various means, such as ingestion or dermal absorption. It is a concern that the combined exposure could cause serious effects even in small doses.

In canned foods, the chemical is made into an epoxy resin to provide a …

Nicotine And What Else?: Hplc Elution Optimization For The Analysis Of Alkaloids Found In Electronic Cigarettes, Jessica L. Murray

Honors Theses

Electronic cigarettes, or e-cigarettes, have been scrutinized by the Food and Drug Administration and other public health organizations for issues related to quality control and efficacy. Erratic nicotine delivery and numerous toxic compounds in refill solutions have been reported. The ultimate goal of this research is to add to the growing amount of knowledge regarding e-cigarette ingredient content, safety, and quality. Standards of the tobacco alkaloids nicotine, anabasine, cotinine, and myosmine were prepared and quantified using high performance liquid chromatography (HPLC). Various elution schemes were tested and adjusted for optimal analyte resolution, and a final elution scheme was developed to …

Purple Urine Bag Syndrome: Regulation Of Pyrimidine Enzymes, Ashley N. Broadway

Honors Theses

Purple Urine Bag Syndrome, PUBS, is a unique condition that shows an interesting discoloration of the urine from women who have a chronic catheter. This study focused on the regulation of enzyme activities to determine the effects that may create an environment where PUBS is seen in patients with catheters. In this study, the reductive pyrimidine pathway was used to read out the bacteria Pseudomonas aeruginosa ATCC 15692. This microorganism expresses a pathway that synthesizes indoxyl from tryptophan. The bacteria strains were grown using various carbon and nitrogen sources. Concentrations of acetonitrile at 2 mM and 10 mM, concentrations of …