Chemistry Commons^™

Contribution Of New Thiol Antioxidant In The Treatment Of Acetaminophen Toxicity, Ahdab Naeem Khayyat

Doctoral Dissertations

"Acetaminophen (N-acetyl-p-aminophenol, APAP) is one of the most widely used over-the-counter antipyretic analgesic medications. It is safe at therapeutic doses, but an overdose can result in severe hepato-nephrotoxicity, a leading cause of drug-induced acute liver failure in the U.S. Although a few different mechanisms have been proposed for APAP-induced toxicity, a significant amount of evidence has pointed to the potential involvement of oxidative stress in acetaminophen toxicity. Depletion of glutathione (GSH) is one of the initiating steps in APAP-induced toxicity; therefore, one strategy for restricting organ damage is to restore GSH levels by using GSH prodrugs like N-acetylcysteine (NAC). Although …

Regional Effects Of Streptozotocin-Induced Diabetes On Shortening And Calcium Transport In Epicardial And Endocardial Myocytes From Rat Left Ventricle, Manal M.A. Smaill, Muhammad A. Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Vadym Sydorenko, Alya Arabi, Frank C. Howarth, Lina Al Kury

All Works

© 2016 The Authors. In the heart, the left ventricle pumps blood at higher pressure than the right ventricle. Within the left ventricle, the electromechanical properties of ventricular cardiac myocytes vary transmurally and this may be related to the gradients of stress and strain experienced in vivo across the ventricular wall. Diabetes is also associated with alterations in hemodynamic function. The aim of this study was to investigate shortening and Ca2+ transport in epicardial (EPI) and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)-induced diabetic rat. Shortening, intracellular Ca2+ and L-type Ca2+ current (ICa,L) were measured by video detection, …

Characterization Of Dielectric Barrier Discharge Atmospheric Air Plasma Treated Chitosan Films, Shashi Pankaj, Carmen Bueno-Ferrer, Luke O'Neill, B.K. Tiwari, Paula Bourke, Patrick J. Cullen

Articles

Dielectric barrier discharge (DBD) plasma is a novel non-thermal food decontamination technology. The effects of DBD plasma on the surface topography, chemical composition and crystal structure, film hydrophilicity, water vapor permeability and oxygen permeability of chitosan films have been examined. DBD plasma treatment increased the surface roughness of chitosan films with emergence of sharp protuberances. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy spectra confirm a significant increase in the oxygen containing groups in the chitosan film after plasma treatment. Significant increase in the film hydrophilicity was observed after plasma treatment. X-ray diffraction results showed that DBD plasma treatment do …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

Direct Phenotypic Screening In Mice: Identification Of Individual, Novel Antinociceptive Compounds From A Library Of 734 821 Pyrrolidine Bis-Piperazines, Richard A. Houghten, Michelle L. Ganno, Jay P. Mclaughlin, Colette T. Dooley, Shainnel O. Eans Torrey Pines Institute For Molecular Studies, Radleigh Santos, Travis Lavoi, Adel Nefzi, Greg Welmaker, Marc A. Giulianotti, Lawrence Toll

Mathematics Faculty Articles

The hypothesis in the current study is that the simultaneous direct in vivo testing of thousands to millions of systematically arranged mixture-based libraries will facilitate the identification of enhanced individual compounds. Individual compounds identified from such libraries may have increased specificity and decreased side effects early in the discovery phase. Testing began by screening ten diverse scaffolds as single mixtures (ranging from 17 340 to 4 879 681 compounds) for analgesia directly in the mouse tail withdrawal model. The “all X” mixture representing the library TPI-1954 was found to produce significant antinociception and lacked respiratory depression and hyperlocomotor effects using …

Synthesis Of Medicinally Relevant Thiazolyl Aryl Ketones Under Mild Conditions, Danielle M. Gardner

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose: The growing amount of clinical resistance observed in current antifungal drugs and in anti-HIV pharmaceuticals is a concern in the medical community. The purpose of this study is to develop a mild synthetic process for biomedically relevant thiazolyl aryl ketones that can be used to develop antifungal and anti-HIV drugs. We hypothesized that the proposed synthetic technique would be more efficient, produce fewer unwanted byproducts, and be more tolerant of functional groups than existing methods.

Methods: Prior to each of the ketone reactions, the necessary salt was synthesized by mixing thiazole and 9-bromofluorene neat in a reaction tube heated …

Design And Synthesis Of Novel Chloroquine-Based Antimalarials, Kevin Vincent Murphy

Dissertations and Theses

Malaria is an infectious, often fatal disease that afflicts nearly 200 million people every year. The disease, characterized by recurring and extreme flu-like symptoms, is caused by the protozoan parasite Plasmodium falciparum. Victims usually contract the disease through a mosquito vector. Chloroquine is a chemotherapeutic that was introduced in the 1940s. For many years the drug was the foremost treatment of malaria, being effective and producing few side effects. Unfortunately, tolerance to chloroquine developed when the parasite evolved a resistance mechanism. Newer drugs have been developed and implemented, but these medicines also show a decreasing effect with continued administration. …

Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce

Chemistry Faculty Research

Purpose

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design

The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results

We observed a profound alteration in the self …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Using Water–Solvent Systems To Estimate In Vivo Blood–Tissue Partition Coefficients, Andrew Lang, Caitlin E. Derricott

College of Science and Engineering Faculty Research and Scholarship

Background: Blood–tissue partition coefficients indicate how a chemical will distribute throughout the body and are an important part of any pharmacokinetic study. They can be used to assess potential toxicological effects from exposure to chemicals and the efficacy of potential novel drugs designed to target certain organs or the central nervous system. In vivo measurement of blood–tissue partition coefficients is often complicated, time-consuming, and relatively expensive, so developing in vitro systems that approximate in vivo ones is desirable. We have determined such systems for tissues such as brain, muscle, liver, lung, kidney, heart, skin, and fat. Results: Several good (p < 0.05) blood–tissue partition coefficient models were developed using a single water– solvent system. These include blood–brain, blood–lung, blood–heart, blood–fat, blood–skin, water–skin, and skin permeation. Many of these partition coefficients have multiple water–solvent systems that can be used as models. Several solvents—methylcyclohexane, 1,9-decadiene, and 2,2,2-trifluoroethanol—were common to multiple models and thus a single measurement can be used to estimate multiple blood–tissue partition coefficients. A few blood–tissue systems require a combination of two water–solvent partition coefficient measurements to model well (p < 0.01), namely: blood–muscle: chloroform and dibutyl ether, blood–liver: N-methyl-2-piperidone and ethanol/water (60:40) volume, and blood–kidney: DMSO and ethanol/water (20:80) volume. Conclusion: In vivo blood–tissue partition coefficients can be easily estimated through water–solvent partition coefficient measurements.

Cladribine Analogues Via O6-(Benzotriazolyl) Derivatives Of Guanine Nucleosides, Sakilam Satishkumar, Prasanna K. Vuram, Siva Subrahmanyam Relangi, Venkateshwarlu Gurram, Hong Zhou, Robert J. Kreitman, Michelle M. Martínez Montemayor, Lijia Yang, Muralidharan Kaliyaperumal, Somesh Sharma, Narender Pottabathini, Mahesh K. Lakshman

Publications and Research

Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic …

Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Microglial cells in the brains of Alzheimer's patients are known to be recruited to amyloid-beta (Aβ) plaques where they exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. In this study, we show that microglia stressed by exposure to sodium arsenite or Aβ(1–42) peptides or fibrils form ex- tensive stress granules (SGs) to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of SGs, is active within the resulting SGs and stimulates the production of reactive oxygen and nitrogen species that are toxic to neuronal cells. This sequestration of SYK inhibits the ability of microglial …

Formaldehyde From E-Cigarettes - It's Not As Simple As Some Suggest, James F. Pankow, Robert M. Strongin, David H. Peyton

Chemistry Faculty Publications and Presentations

The Authors address critics of a previously published letter to the Editor in The New England Journal of Medicine, pertaining to hidden formaldehyde in E-Cigarette aerosols and the need for future testing of their safety.

Plasminogen Activator Inhibitor-1 Inhibitors And Methods Of Use Thereof To Modulate Lipid Metabolism, Daniel A. Lawrence, Cory Emal, Jacqueline Cale, Enming Joe Su, Mark Warnock, Shih-Hon Li, Jeanne Ann Cupp

Patents

The invention relates to plasminogen activator-I (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or condition associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to modulate lipid metabolism and treat conditions associated with elevated PAI-1, cholesterol, or lipid levels.

Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne

Pharmacy Faculty Articles and Research

The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …

Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting …

Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polyrotaxanes are polymers that have macrocycles threaded onto them, analogous to beads threaded onto a string. These materials are used for a variety of different biomedical applications.^1-3 The Thompson group has been developing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) polyrotaxanes as therapeutics for the treatment of Niemann-Pick Type C (NPC) disease. NPC is a debilitating genetic disorder where cholesterol accumulates in the lysosomes of cells.⁴ Developing a scalable process is crucial for the advancement of these materials as NPC therapeutics. The goal of this project is to optimize the only protocol for the synthesis of HP-β-CD/Pluronic polyrotaxanes in order to develop a …

Plasminogen Activator Inhibitor-1 Inhibitors And Methods Of Use Thereof To Modulate Lipid Metabolism, Daniel A. Lawrence, Dudley Strickland, Jacqueline Cale, Enming Joe Su, Cory Emal, Mark Warnock

Patents

The invention relates to plasminogen activator-I (PAI-1) inhibitor compounds and uses thereof in the treatment of any disease or condition associated with elevated PAI-1. The invention includes, but is not limited to, the use of such compounds to modulate lipid metabolism and treat conditions associated with elevated PAI-1, cholesterol, or lipid levels.

Synthesis And Flammability Testing Of Epoxy Functionalized Phosphorous-Based Flame Retardants, Vladimir Benin, Xuemei Cui, Alexander Morgan, Karl Seiwert

Chemistry Faculty Publications

Several potential new phosphorus-containing flame retardant molecules were evaluated for heat release reduction potential by incorporation of the molecules into a polyurethane, generated from methylene diphenyl diisocyanate and 1,3-propane diol. The heat release reduction potential of these substances was evaluated using the pyrolysis combustion flow calorimeter (PCFC). The polyurethanes were prepared in the presence of the potential flame retardants via solvent mixing and copolymerization methods to qualitatively evaluate their potential reactivity into the polyurethane prior to heat release testing. The functionality of the flame retardants was epoxide based that would potentially react with the diol during polyurethane synthesis. Flammability testing …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

Diol-Mediated Versus Water-Mediated Proton Transfer Reactions, Angela Moses

DePaul Discoveries

The triple-proton-transfer reactions of 8H-1,8-naphthyridin-2-one (8H-naph) have been investigated by employing different ab initio quantum mechanical methods. The proton transfer reactions studied were facilitated through an adjacent 1,3-propanediol molecule or two adjacent water molecules. Identical proton transfer reactions were studied using a model system of 8H-naph to investigate the validity of computational approaches that use model systems to study more complex systems. The solvent effects on the structures were investigated for comparison to the initial gas phase calculations. The potential energy, reaction force, and work profiles were studied along the intrinsic reaction coordinate to monitor the developing proton transfer reactions.

Do Oaks With A Provenance Related To Warmer Climates Emit More Isoprene?, Elizabeth Carter

DePaul Discoveries

The hydrocarbon isoprene plays an important role in atmospheric chemistry, particularly in regards to air pollution and climate change. It is important to know why certain plant species emit isoprene and what factors affect its production in order to predict future air quality. Past research has indicated that isoprene aids in coping with heat stress, so it was hypothesized that source latitude (a proxy for climate) would significantly impact isoprene production by oaks grown in a common location. Twelve bur oaks collected from a latitudinal range (30-45˚) and raised at the Morton Arboretum were assayed for their isoprene emission rate …

A Study Whether Humans Can Produce Free Fatty Acids For Tasting, Emily Bacher

Student Scholarship

A growing concern throughout the world, especially the United States, is the health of our population. According to the National Health and Nutrition Examination Survey (NHANES) performed in 2009-2010, approximately 35% of both men and women in the United States are obese (Flegal, 2012). In 2005, more than 300,000 deaths in the United States were attributed to obesity. However, the World Health Organization listed obesity as one of ten most preventable health risks (Wilborn, 2005).
Why, then, do we as a society struggle so much with our weight? Some, such as Swinburn, believe this trend of obesity can be attributed …

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.^[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. ^[1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.^[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. ^[3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …

The Use Of Shape Memory Polymers As A Tool To Study Human Fibrosarcoma And Murine Mesenchymal Stem Cell Migration, Justin N. Elkhechen

Renée Crown University Honors Thesis Projects - All

Shape memory polymers (SMPs) are a class of “smart” materials that can transform between two distinct conformations through external stimuli, such as heat or electricity. Their usage in bioengineering has led to a promising field of research that lies at the interface of cell and mechanobiology, potentially providing insight into cancer therapies and tissue development—two processes that exist in dynamic environments in vivo. The present work involves creating new, shape changing, scaffolds for studies to analyze cell migration upon changes to the environmental topography. Specifically, this Capstone has been primarily focused on the development of a “half and half” fibrous …

Distributed Drug Discovery: Synthesis Of Unnatural Amino Acids As Potential Antimalarial Drugs, Amanda Dugan

Honors College

Through the collaboration of many institutions across the globe, the Distributed Drug Discovery project founded at Indiana University-Purdue University Indianapolis seeks to aid in the development of drugs for the developing world. In response to two antimalarial assay hits, our team at Abilene Christian University has synthesized many unnatural amino acid analogs using resin-based combinatorial chemistry. Proton nuclear magnetic resonance spectroscopy has been used to characterize the compounds and thin layer chromatography to determine purity. All compounds were purified on hypersep cyanosilica columns.

Urine Proteomics Identifies Preeclampsia Subphenotypes, Michelle R. Axe

Undergraduate Honors Thesis Projects

Preeclampsia is a perinatal complication of unknown etiology, resulting in 76,000 maternal deaths and 500,000 infant deaths annually₁. The Nationwide Children’s Center for Perinatal Research was the first cohort to propose that preeclampsia is rooted in protein misfolding. We aimed to characterize the misfolded protein components of maternal urine samples and to determine if distinct molecular profiles exist for clinical preeclampsia phenotypes. A total of 86 maternal urine samples from Yale-New Haven Hospital were analyzed for this study, from six clinical preeclampsia subphenotypes- pregnant control (n=10), idiopathic proteinuria (n=15), mild preeclampsia (n=14), superimposed preeclampsia (n=12), typical severe preeclampsia …

Flavour Chemicals In Electronic Cigarette Fluids, Peyton A. Tierney, Clarissa D. Karpinski, Jessica E. Brown, Wentai Luo, James F. Pankow

Chemistry Faculty Publications and Presentations

Background: Most e-cigarette liquids contain flavour chemicals. Flavour chemicals certified as safe for ingestion by the Flavor Extracts Manufacturers Association may not be safe for use in e-cigarettes. This study identified and measured flavour chemicals in 30 e-cigarette fluids.

Methods: Two brands of single-use e-cigarettes were selected and their fluids in multiple flavour types analysed by gas chromatography/mass spectrometry. For the same flavour types, and for selected confectionary flavours (eg, bubble gum and cotton candy), also analysed were convenience samples of e-cigarette fluids in refill bottles from local ‘vape’ shops and online retailers.

Results: In many liquids, total flavour chemicals …

Essential Oils From Apple Mint (Mentha Suaveolens) And Passionflower Fruit (Passiflora Incarnata): Studies On Cognition, Coordination, And Chemical Components., Evelyn F. Patrick *, Jessie Bowers *, Shannon Read *, Brett R. Lackey, Christine Murphy, Sandra L. Gray

Journal of the South Carolina Academy of Science

Plant essential oils (EO) are used as perfumes, lotions and air fresheners because of their pleasant aromas, but EO also have the ability to elicit changes in mood and behavior. These activities are influenced by the mode of administration and by multiple signaling pathways. The EO aromas from organically grown apple mint (Mentha suaveolens) and passionflower fruit (Passiflora incarnata) were assessed for their effects on cognition and coordination. Participants completed two tasks designed to test working memory and bimanual task efficiency in rooms infused with apple mint, passionflower fruit or control EO. Bimanual coordination was assessed using the Intercept2 program …