Chemicals and Drugs Commons^™

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …

Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt

University of New Orleans Theses and Dissertations

Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.

Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells. By …

Carbon Dots As Artificial Peroxidases For Analytical Applications, Shih-Chun Wei, Yang-Wei Lin, Huan-Tsung Chang

Journal of Food and Drug Analysis

Nanozymes have become attractive in analytical and biomedical fields, mainly because of their low cost, long shelf life, and less environmental sensitivity. Particularly, nanozymes formed from nanomaterials having high surface area and rich active sites are interesting since their activities can be tuned through carefully controlling their size, morphology, and surface properties. This review article focuses on preparation of carbon dots (C dots) possessing peroxidase-like activity and their analytical applications. We highlight the important roles of the oxidation states and surface residues of C dots and their nanocomposites with metal, metal oxides, or metal sulfides playing on determining their specificity …

Design And Synthesis Of Novel No-Drug Hybrid Compound And Green Catalytic Activity Evaluation Of Synthesized Silver Nanoparticles-Halloysite Nanocomposite, Majed Abdullah Bajaber

University of New Orleans Theses and Dissertations

Acetaminophen is a well-known analgesic that can manage pain and reduce fever. SCP-1 is a derivative of acetaminophen that showed significantly reduced hepatotoxicity and nephrotoxicity comparative to acetaminophen. Nitric oxides have been well known to play a key role in a wide variety of physiological and pathophysiological important processes. It was therefore of interest to synthesize a nitric oxide donor linked to SCP-1 that could have enhanced analgesic and antipyretic activity. A furoxan CAS 1609 as NO-donor was synthesized and linked to SCP-1 successfully. The furoxan CAS 1609 was initially synthesized from tetronic acid to give 1,2- dioxime in 86 …

Nuclear-Targeted Gold Nanoparticles Enhance The Effects Of Radiation Therapy With And Without Liposomal Delivery, Maureen Aliru

Dissertations & Theses (Open Access)

Less that 10% of pancreatic cancer patients are eligible for curative resection, and clinical trials evaluating chemoradiation in locally advanced patients with unresectable disease have been largely disappointing. New and creative therapeutic approaches are needed to address the unment need for treatment options. The objective of this thesis is to advance radiosensitization of treatment-resistant densely desmoplastic pancreatic cancer using nanoparticles to surmount biological barriers to effective particle distribution for DNA-targeting.

Clinical translation of radiosensitizing nanoparticles has stalled owing to technical challenges. Current strategies to use AuNPs for radiosensitization require large quantities of gold, kilovoltage x-rays, immediate irradiation after intravenous administration, …

Coevolution, Dynamics And Allostery Conspire In Shaping Cooperative Binding And Signal Transmission Of The Sars-Cov-2 Spike Protein With Human Angiotensin-Converting Enzyme 2, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Binding to the host receptor is a critical initial step for the coronavirus SARS-CoV-2 spike protein to enter into target cells and trigger virus transmission. A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of …

Nicotine In Tobacco Product Aerosols: 'It's Deja Vu All Over Again', Anna K. Duell, James F. Pankow, David H. Peyton

Chemistry Faculty Publications and Presentations

Introduction: The distribution of nicotine among its free-base (fb) and protonated forms in aerosolised nicotine affects inhalability. It has been manipulated in tobacco smoke and now in electronic cigarettes by the use of acids to de-freebase nicotine and form ‘nicotine salts’.

Methods: Measurements on electronic cigarette fluids (e-liquids) were carried out to determine (1) the fraction of nicotine in the free-base form (α fb) and (2) the levels of organic acid(s) and nicotine. Samples included JUUL ‘pods’, ‘look-a-like/knock-off’ pods and some bottled ‘nicotine salt’ and ‘non-salt’ e-liquids.

Results: α fb= 0.12 ±0.01 at 40°C (≈ 37°C) for 10 JUUL products, …

Single‐Molecule 3d Orientation Imaging Reveals Nanoscale Compositional Heterogeneity In Lipid Membranes, Jin Lu, Hesam Mazidi, Tianben Ding, Oumeng Zhang, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

In soft matter, thermal energy causes molecules to continuously translate and rotate, even in crowded environments, thereby impacting the spatial organization and function of most molecular assemblies, such as lipid membranes. Directly measuring the orientation and spatial organization of large collections (>3000 molecules μm⁻²) of single molecules with nanoscale resolution remains elusive. In this paper, we utilize SMOLM, single‐molecule orientation localization microscopy, to directly measure the orientation spectra (3D orientation plus “wobble”) of lipophilic probes transiently bound to lipid membranes, revealing that Nile red's (NR) orientation spectra are extremely sensitive to membrane chemical composition. SMOLM images resolve …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations & Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Drug Delivery In Catheterized Arterial Blood Flow With Atherosclerosis, Saulo Orizaga, Daniel N. Riahi, Jose R. Soto

School of Mathematical and Statistical Sciences Faculty Publications and Presentations

We study the problem of drug delivery in a catheterized artery in the presence of atherosclerosis. The problem is modeled in the context of a two-phase flow system which consists of red blood cells and blood plasma. The coupled differential equations for fluid (plasma) and particles (red cells) are solved for the relevant quantities in the reasonable limits. The drug delivery problem is modeled with a partial differential equation that is developed in terms of the drug concentration, blood plasma velocity, hematocrit value and the diffusion coefficient of the drug/fluid. A conservative-implicit finite difference scheme is develop in order to …

Structural Analysis Of Protein Therapeutics Using Covalent Labeling – Mass Spectrometry, Patanachai Limpikirati

Doctoral Dissertations

Using mass spectrometry (MS) to obtain information about a higher order structure of protein requires that a protein’s structural properties are encoded into the mass of that protein. Covalent labeling (CL) with reagents that can irreversibly modify solvent accessible amino acid side chains is an effective way to encode structural information into the mass of a protein, as this information can be read-out in a straightforward manner using standard MS-based proteomics techniques. The differential reactivity of proteins under two or more conditions can be used to distinguish protein topologies, conformations, and/or binding sites. CL-MS methods have been effectively used for …

Synthesis, Characterisation And Biological Evaluation Of Tyramine Derived Schiff Base Ligand And Its Transition Metal(Ii) Complexes, Abdul Khader Jailani, N.S.K. Gowthaman, Mookkandi Palsamy Kesavan

Karbala International Journal of Modern Science

In this study, a new tyramine derived Schiff base ligand (L) (L=1,3-phenylene-bis-4-aminoantipyrinyl-4-aminoethylphenol) and its derived transition metal(II) complexes [Cu(L)Cl₂](1), [Ni(L)Cl₂](2), [Co(L)Cl₂] (3) and [Zn(L)Cl₂] (4) have been synthesized and well characterized by the way of different spectroscopic and analytical techniques. Analytical and spectroscopic studies result suggests that metal(II) complexes more probably have octahedral geometry. DNA binding tendency of L and metal(II) complexes 1-4 have been assessed by probing their ability to bind with Calf Thymus DNA (CT-DNA) via electronic absorption and cyclic voltammetry titration methods. The results clearly reveal that the metal(II) …

Gama-Lactams And The Reformatsky Reaction: New Tricks For Old Chemistry, Dylan Dupont

Honors Theses

DUPONT, DYLAN. An Alternative Synthetic Pathway to γ-Lactam Compounds

Through the Application of Novel Reformatsky-Type Chemistry. Department

of Chemistry, June 2020

ADVISOR: James C. Adrian Jr. Ph.D.

It is the intent of the present report to relate the results of our attempt to elucidate and optimize a novel preparation of γ-lactam compounds. To achieve this end, it is proposed that the use of novel Reformatsky-type chemistry may provide a viable means. Generally, it has herein been validated that employment of α-amino ketones in traditional Reformatsky chemistry will form the traditional Reformatsky ester-adduct, and that this adduct is capable of spontaneously …

Designing Peptides To Bind Kappa B Dna And Mimic Nf-Kappa B Protein Complexes, Nicholas A. Markowich

Honors College Theses

Transcription factors are important proteins that regulate gene expression and protein synthesis. Transcription factors can either boost the gene’s transcription rate by helping RNA polymerase activate transcription or restrict it by interfering with RNA polymerase, thereby repressing transcription. Nuclear factor-kappa-B (NF-κB) transcription factors are a family of proteins that control the synthesis of proteins involved in many cellular processes such as inflammatory and immune responses, cell growth, and apoptosis. However, the overexpression and activation of these transcription factors is linked to deadly conditions such as cancer and neurodegenerative diseases which currently have few safe cures. The goal of this research …

I. Non-Degradable Polysiloxane Networks For Controlled Release Applications, And Ii. Additive Free, Degradable Silyl-Ether Furyl-Maleimide Networks, Caleb M. Bunton

Chemistry Theses and Dissertations

I. Two different series of non–degradable polysiloxane networks were prepared for the encapsulation and controlled release of a small molecule agent. For the first series, hydrosilylation was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and silylhydride functional poly(dimethyl)siloxanes. For the second series, the thiol-ene reaction was utilized to prepare networks of varying crosslink densities, as determined from swelling studies, from vinyl terminated and mercaptopropyl functional poly(dimethyl)siloxanes. Nile red dye was used as an encapsulated agent and dye release from each series of networks was measured using UV–vis spectroscopy to determine controllability …

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 …

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 …

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 …

The Effects Of Zoledronate And Sleep Deprivation On The Distal Femur Trabecular Thickness Of Ovariectomized Rats: Application Of Different Statistical Methods, Erin Nolte

Student Scholar Symposium Abstracts and Posters

Osteoporosis is a disease that causes the degradation of bone, leading to an increased risk of fracture. 1 in 3 women over the age of 50 will be affected by Osteoporosis. This study aims to understand how bone is affected by sleep deprivation in estrogen-deficient rats, and how Zoledronate might negate the inimical effects of sleep deprivation on bone. As bone mineral density (BMD) is a crude evaluation of the architectural changes seen in Osteoporosis, trabecular thickness may serve as a better single evaluation of bone health. 31 Wistar female rats were ovariectomized and separated into 4 random groups. The …

Characterization Of Dimerization Domains On The Mannose-6-Phosphate/Insulin-Like Growth Factor 2 Receptor, Tyler Degener

UNO Student Research and Creative Activity Fair

The mannose-6-phosphate/insulin-like growth factor 2 (M6P/IGF2) receptor is a transmembrane protein with the ability to sequester growth factors from the extracellular matrix. This behavior links the receptor to tumor suppression. On a structural level, the extracellular portion of the protein is segmented into 15 homologous repeats, which can be divided further into 5 triplet domains, labelled 1-3, 4-6, 7-9, 10-12, and 13-15. Each triplet receptor displays its own unique ligand binding affinity, including the ability to form dimers with triplets on a second M6P/IGF2 receptor. In fact, previous studies indicate that this protein functions optimally when dimerized. Thus, the purpose …

Analysis Of Oxidatively Damaged Proteins By Mass Spectrometry, Vincent Saullo

Electronic Thesis and Dissertation Repository

As humans age, exposure to oxidative stress may induce protein degradation or aggregation; both resulting in loss of protein function. Protein oxidative damage remains a dominant pathology in many common ailments. To combat these pathologies, scientists must understand the nature of oxidative modifications and their effects on protein structure and dynamics. This work employs a range of mass spectrometry (MS) methods to characterize and analyze the effects of oxidative damage on the model protein myoglobin (Mb). Mb was oxidized using tert-butyl hydroperoxide, and the resulting modifications were characterized by top-down and bottom-up MS workflows. Hydrogen/deuterium exchange MS indicated elevated structural …

Singlet Oxygen Generation By Porphyrins And Metalloporphyrins Revisited: A Quantitative Structure-Property Relationship (Qspr) Study, Andrey A. Buglak, Mikhail Filatov, Althaf M. Hussain, Manabu Sugimoto

Books/Book chapters

state followed by formation of singlet oxygen (1O2), which is a highly reactive species and mediates various oxidative processes. The design of advanced sensitizers based on porphyrin compounds have attracted significant attention in recent years. However, it is still difficult to predict the efficiency of singlet oxygen generation for a given structure. Our goal was to develop a quantitative structure-property relationship (QSPR) model for the fast virtual screening and prediction of singlet oxygen quantum yields for pophyrins and metalloporphyrins. We performed QSPR analysis of a dataset containing 32 compounds, including various porphyrins and their analogues (chlorins and bacteriochlorins). Quantum-chemical descriptors …

Stimuli-Responsive Gelators From Carbamoyl Sugar Derivatives And Their Responses To Metal Ions And Tetrabutylammonium Salts, Dan Wang, Anji Chen, Joedian Morris, Guijun Wang

Chemistry & Biochemistry Faculty Publications

Carbohydrate-based low molecular weight gelators (LMWGs) are interesting compounds with a variety of applications. In this research, a library of nineteen carbamate derivatives of N-acetyl-D-glucosamine were synthesized and characterized, and several derivatives were found to be effective LMWGs. They formed gels in pump oils as well as mixtures of water with ethanol or water with DMSO. The structures of the carbamoyl chains played an important role in the gelation properties, short chain aliphatic derivatives and phenyl carbamates formed gels in more solvents than certain aromatic and dimeric carbamates. The phenyl carbamate gelator was also selected for the encapsulation of …

Contemporary Epidemiology Of Rising Atrial Septal Defect Trends Across Usa 1991–2016: A Combined Ecological Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal? Methods: Geospatiotemporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Antifungal Defense Molecules From Bacterial Symbionts Of North American Trachymyrmex Ants, Georgia Scherer

CMC Senior Theses

Defensive symbioses, in which microbes provide molecular defenses for an animal host, hold great potential as untapped sources of therapeutically useful antibiotics. Fungus-growing ants use antifungal defenses from bacterial symbionts to suppress pathogenic fungi in their nests. Preliminary chemical investigations of symbiotic bacteria from this large family of ants have uncovered novel antifungal molecules with therapeutic potential, such as dentigerumycin and selvamicin.

In this study, the bacterial symbionts of North American Trachymyrmex fungus-growing ants are investigated for antifungal molecules. Plate-based bioassays using ecologically-relevant fungal pathogens confirmed that these bacteria have antifungal activity. In order to purify and identify the antifungal …

Development Of A Method For The Detection And Quantification Of Various Benzodiazepines And Z-Drugs In Human Blood And Qualitative Identification In Urine Samples Using Liquid Chromatography Mass Spectrometry (Lc-Ms/Ms), Haley Michel

Williams Honors College, Honors Research Projects

This method developed in the toxicology department at the Cuyahoga County Medical Examiner’s Office (CCMEO) detects 40 benzodiazepines and metabolites along with several z-drugs in blood and urine by liquid chromatography tandem mass spectrometry. A sample amount of 0.5 mL was used to detect analytes in postmortem drug facilitated sexual assault and impaired driving cases. Twenty-nine analytes met criteria for quantification while the remaining 14 were used as qualitative indicators. Bias and precision results for quality controls met criteria, staying within ±15% except for clonazolam and etizolam which were within ±20%. Quantitative reporting criteria which included dilution integrity was met …