Chemicals and Drugs Commons^™

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Synthesis Of Fluoroorganics And Applications Of Novel Fluorinated Building Blocks, Wei Wei

Dissertations, Theses, and Capstone Projects

Diastereoselectivity of fluorination of a carbanion alpha to a sulfone in enantiomerically pure N-Boc protected (R)- and (S)-2,2-dimethyl-4-((arylsulfonyl)methyl)oxazolidines has been studied. Fluorination proceeded with good to excellent diastereoselectivity, which was base-dependent and was highest with lithium diisopropylamide (LDA). Diastereoselectivity also depended on the aryl moiety of the aryl sulfone and was highest with benzothiazole-derived sulfones. Under basic conditions, epimerization at the C–F stereogenic center alpha to the sulfone has been achieved for the first time and proceeded with good to excellent diastereoselectivity, which was highest in the case of a benzothiazole sulfone and with a lithium base. …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Elisa Validation Method For The Detection Of Ketamine In Hair, Daria A. Centonza

Student Theses

An ELISA method was developed and validated to detect ketamine in human hair samples. Ketamine is an anesthetic drug that causes memory loss, dissociative sensations, and hallucinations. Due to these adverse effects, ketamine is a common drug used in drug facilitated sexual assaults (DFSAs). It is very important to be able to detect the substances used in DFSAs over a longer period of time due to the delayed reporting of these crimes. Victims, often out of fear and from the sedative/memory loss effects of the drugs, tend to report these crimes when it is too late to use urine and …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

Synthesis, Characterization And Applications Of Peptide-Coated Nanoparticles, Mina Sadat Poursharifi

Dissertations, Theses, and Capstone Projects

Ovarian Cancer (OC) is the most lethal female malignancy worldwide, mainly due to its high recurrence rate and poor diagnosis. Most patients present with late stage of the disease, and less than 25% of patients survive the five years mark. Nanotherapy provides significant and unique benefits for drug efficacy, as nanoparticles (NPs) can increase the solubility, bioavailability, and permeability of many potent drugs. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers used in NPs formulations, mainly due to its biocompatibility and biodegradability. Polyethylene glycol (PEG) is one of the most commonly used moieties to prolong the NPs …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

The Structural And Functional Role Of Photosensing In Rgs-Lov Proteins, Zaynab Jaber

Dissertations, Theses, and Capstone Projects

Light provides organisms with energy and spatiotemporal information. To survive and adapt, organisms have developed the ability to sense light to drive biochemical effects that underlie vision, entrainment of circadian rhythm, stress response, virulence, and many other important molecularly driven responses. Blue-light sensing Light-Oxygen-Voltage (LOV) domains are ubiquitous across multiple kingdoms of life and modulate various physiological events via diverse effector domains. Using a small molecule flavin chromophore, the LOV domain undergoes light-dependent structural changes leading to activation or repression of these catalytic and non-catalytic effectors. In silico analyses of high-throughput genomic sequencing data has led to the marked expansion …

Synthesis And Evaluation Of C-10 Nitrogenated Aporphine Alkaloids At Serotonin And Dopamine Receptors, Anupam Karki

Dissertations, Theses, and Capstone Projects

Aporphine alkaloids, belonging to the isoquinoline class of compounds, have been investigated as a potential source of ligands for Central Nervous System (CNS) receptors. Previous research indicates that the aporphine scaffold may be manipulated to synthesize selective ligands for serotonin and dopamine receptors. Novel aporphine alkaloids containing C10 nitrogen substitutions were synthesized, and their affinities were evaluated at serotonin (5-HT1A, 5-HT1B, 5-HT2A, 5-HT7A) receptors and dopamine (D1, D2, D3, D4, and D5) receptors. Two series of racemic aporphine compounds with C10 nitrogenous functionalities were synthesized and analyzed at the aforementioned receptors. The first series of aporphine alkaloids contain C10 nitro, …

Design, Synthesis And Evaluation Of Molecules With Selective And Poly-Pharmacological Actions At D1r, D3r And Sigma Receptors, Pierpaolo Cordone

Dissertations, Theses, and Capstone Projects

The dopamine D3 receptor (D3R) is one of the most studied receptors involved in drug addiction. One of the most common strategies to treat substance use disorders is via D3R antagonism. The majority of the D3R antagonists synthesized so far have poor pharmacokinetic properties and/or lack selectivity toward D3R. In this thesis, the design, synthesis and biological evaluation of novel molecules that target the dopamine D1 receptor (D1R), D3R and the serendipitous discovery of molecules that target s receptors will be described.

Chapter 1 presents a survey of the fundamental pharmacology of D1R, D3R and s receptors and the therapeutic …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Analysis Of Newspaper Coverage Of Psilocybin From January 1, 1989 To December 31, 2019, Dax Oliver

Dissertations, Theses, and Capstone Projects

Psilocybin is a chemical compound that has received a lot of attention from medical researchers in recent years. However, this research is not merely a medical issue but a social and political one as well. In the 1960s, psilocybin and other psychedelic compounds were widely ingested outside of clinical settings. This alarmed some of the American public, resulting in severe legal restrictions on psilocybin use and research.

Today, many psilocybin advocates hope that it will avoid the negative public sentiment of the 1960s. To help gauge public sentiment about other psychoactive compounds, some studies have examined newspaper coverage, but there …

Nature-Inspired Electrode Materials For Next Generation Sustainable Energy Storage, Mikhail Miroshnikov

Dissertations, Theses, and Capstone Projects

Despite revolutionizing the world of portable electronics, the contemporary lithium-ion battery (LIB) suffers from challenges associated with the cost, safety, and environmental impact of transition metal oxide-based intercalation cathodes. To alleviate these issues, naturally occurring organic molecules may serve as sustainable alternatives to traditional inorganic cathode materials. The electrochemical properties of organic compounds are derived from redox-active functional groups containing oxygen, nitrogen and sulfur. Additionally, these functional groups are capable of coordinating metal ions beyond lithium, allowing for compatibility with sodium-ion batteries (SIBs) and other earth abundant metal-based energy storage systems. However, despite competitive performance against commercialized cathode materials, much …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Simultaneous Determination Of Fourteen Antipsychotic Drugs In Whole Blood By Solid Phase Extraction And Liquid Chromatography Tandem Mass Spectrometry, Theresa M. Dawe

Student Theses

Anti-psychotic drugs are commonly prescribed to patients to treat several mental conditions, such as bipolar, schizophrenia, and manic-depressive disorder. The analysis of anti-psychotic drugs in blood is a common practice in clinical and forensic toxicology, to monitor drug treatment (therapeutic drug monitoring) or to explain the cause of the impairment or intoxication in human performance and in postmortem cases. However, most of the current studies have been performed in plasma, and a limited number in blood. We developed and validated a method to confirm and quantify a panel of commonly prescribed anti-psychotic drugs in whole blood using solid phase extraction …

Determination Of Anxiolytic And Antidepressant Medicines In New York City Wastewater Samples, Jasmine J. Gayle

Student Theses

Wastewater-based epidemiology (WBE) provides information about a population’s exposure to certain chemical agents, such as drugs of abuse and medicines, by the analysis of human biomarkers, also known as excretion products, in wastewater samples. Although this is a growing field worldwide, mainly in Europe, Oceania, and Asia, limited data from the US are currently available. We developed and validated an analytical method to quantitatively and qualitatively determine the presence of commonly prescribed drugs to treat anxiety (alprazolam, buspirone, clonazepam, lorazepam, and propranolol) and depression (bupropion, citalopram, clomipramine, duloxetine, fluoxetine, imipramine, paroxetine, sertraline, and venlafaxine) in wastewater using liquid chromatography tandem …

A Pretargeted Spect Imaging Strategy Employing Technetium-99m Based On Bioorthogonal Diels-Alder Click Chemistry, Justin H. Walsh

Dissertations, Theses, and Capstone Projects

A series of related N₃S ^99mTc-peptide complexes were synthesized and tested for use in pretargeting SPECT imaging that utilizes the bioorthogonal Diels-Alder click reaction between tetrazine (Tz) and transcyclooctene (TCO). The objective was to optimize the excretory pathways of the ^99mTc-peptide complexes for maximum tumor targeting with the in vivo “click” and minimum non-target uptake. The ^99mTc–tetrazine constructs were prepared by reaction of ^99mTc-peptide complexes (^99mTc-FKC, ^99mTc-FKCR, ^99mTc-DKC, and ^99mTc-SKC) with Tz-NHS or Tz-PEG₅-NHS to form ^99mTc FK(Tz)C, ^99mTc-FK(PEG₅-Tz)CR, ^99mTc-DK(PEG₅-Tz)C, …

Heterocycle Synthesis From Quinols, Jing Wu

Dissertations, Theses, and Capstone Projects

Three cascade reactions that provide access to various heterocyclic skeletons from quinols were developed. Various substituted 1-hydroxyacridones, 4-hydroxycarbazoles and 4-hydroxy-indolin-3-ones were readily synthesized in moderate to excellent yields. The common sequential transformation involves carbamation/Michael addition/mixed Claisen condensation/decarboxylative aromatization which were realized in one-pot reactions in the synthesis of acridones and indolin-3-ones, or two-step reactions in the synthesis of carbazoles. A side reaction from oxidative dearomatization of phenols, affording iodo diaryl ethers in one step from commercial phenols, albeit in low yields, revealed an intricate mechanistic pathway. The synthesis of jaboticabin was realized in nine linear steps from commercial phloroglucinol and …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …

An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee

Dissertations, Theses, and Capstone Projects

Cervical cancer remains as one of the most prevalent cancers effecting women globally. Lack of awareness and affordable prophylactic and therapeutic options in developing countries drive the need for alternative low-cost approaches. Dietary polyphenols have gained increased attention as possible anti-cancer agents. Our study aims to investigate whether two natural structural analogs, resveratrol and pterostilbene, exhibit anti-HPV (Human papillomavirus) activity in cervical cancer. To determine the efficacy of these polyphenols, extensive in vitro and in vivo analyses were carried out. For the in vitro studies we utilized human HeLa cells (HPV18 positive) and murine TC1 cells (HPV 16 oncogene positive). …

Unlocking The Mysteries Of Weed And Mexico, Eddy Martinez

Capstones

An American biotech firm named Phylos Bioscience is interested in entering the Mexican marijuana market once it legalizes. Before it can do that, it must deal with the Mexican government and a conservative society.

https://eddymartinezcunyedu.atavist.com/figuring-out-the-mysteries-of-weed-and-mexico

Synthesis And Characterization Of Cytocompatible Sponge-Mimetic Scaffolds And Biomedical Polymers, Kamia Punia

Dissertations, Theses, and Capstone Projects

This dissertation describes the novel synthetic methodologies towards: a) protein/polysaccharide intercalated sponge-mimetic scaffolds for 3D cell culture, b) peptide-mimetic cationic amphiphilic antibacterial polymers, and c) bioactive Poly(DL-lactide-co-glycolide) (PLGA) nanofibers by solution blow spinning for the treatment of cancer and traumatic wound care.

The classic “chemical garden” experiment is reconstructed to produce protein/polysaccharide (ingredients of cyanobacterial origin) intercalated silicate-phosphate tubules that resemble tubular sponges. The constructs were synthesized by seeding calcium chloride into a solution of sodium silicate-potassium phosphate and gelatin/polysaccharides. The morphology and composition of sponge-mimetic tubules were analyzed by a battery of techniques. Bioconjugation and coating protocols were developed …

Zolpidem Facilitated Sexual Assaults: A Hair Method Validation, Danielle N. Chasworth

Student Theses

A liquid chromatography tandem mass spectrometry (LC-MSMS) method was developed and validated to detect for the presence of zolpidem in human hair samples. Zolpidem is a sedative hypnotic whose adverse effects make it a common drug found in drug facilitated crimes (DFC). It is important to be able to detect and quantitate the drug after a long period of time due to the victim’s delayed reporting of the crime. Hair’s long window of detection makes it a useful matrix for DFC investigations. The linear range of the assay was targeted at 2 pg/mg to 1,000 pg/mg and experiments designed to …

Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, Hari K. Akula

Dissertations, Theses, and Capstone Projects

The C4 amide carbonyl of O-t-butyldimethylsilyl-protected thymidine, 2’-deoxyuridine, and 3’-azidothymidine (AZT) was activated by reaction with (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF as solvent. This led to the formation of corresponding O⁴-(benzotriazol-1-yl) derivatives, which are reactive intermediates. Substitution at the C4 position was then carried out by reactions with alkyl and aryl amines, and thiols. Typically, reactions were conducted as a two-step, one-pot transformation, and also as a one-step conversion. After examining the reactions, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

New Dyes For Cancer Theranostics, Waqar Rizvi

Dissertations, Theses, and Capstone Projects

Porphyrinoids are robust heterocyclic dyes studied extensively for applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target disease, modulate photophysical properties, or direct self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results …

Microrna 1207-3p In Prostate Cancer, Dibash Das

Dissertations, Theses, and Capstone Projects

Prostate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines …

Healthy People Are Bad For Capitalism, Eri King

Theses and Dissertations

Healthy People are Bad For Capitalism is a four part installation that creates an alternative space for the chemicals, Red 40 and Monosodium Glutamate. Presented as a holistic center that offers healing services and remedies, Center for the Red 40 and MSG Healing explores the homeopathic doctrine of Like Cures Like (what make a human ill also cures them) through the relationship between Traditional Japanese Healing Practices, and Western Capitalism.

Healthy People are Bad For Capitalism presents Red 40 MSG Apothecary, Red 40 Zen MSG Healing Rock Garden, Theta Wave Eternal Flame Meditation and Red 40 MSG …

Roles Of Gabab, Muscarinic And Nicotinic Receptor Signaling In The Acquisition And Expression Of Fructose And Fat-Conditioned Flavor Preferences And Acquisition Of Quinine-Conditioned Flavor Avoidances In Rats, Francis M. Rotella

Dissertations, Theses, and Capstone Projects

In addition to increased intake of sweet solutions by mammals, learning, particularly classically-conditioned “Pavlovian-like” learning, also plays an important role. An orosensory conditioned flavor preference (CFP) can be elicited by pairing one novel flavor (conditioned stimulus, CS+) with a fructose solution and a second novel flavor (CS-) with a saccharin solution. Rats will prefer the CS+ flavor in a subsequent 2-bottle choice test with both flavors mixed in saccharin. Previous pharmacological analyses revealed that systemic administration of dopamine (DA) D1 and D2 as well as NMDA, but not opioid, receptor antagonists eliminated the acquisition (learning) of fructose-CFP. Further, expression of …