Medicine and Health Sciences Commons^™

Application Of Mass Spectrometry For The Characterization Of Synthetic Oligomers And Natural Lignin, Poorya Kamali

Theses and Dissertations--Chemistry

As part of the ongoing effort to substitute finite fuel and chemical resources with renewable ones, biomass is emerging as one of the most promising sources. Biomass consists of three main components of cellulose, hemicellulose, and lignin. Traditionally, cellulose has been used extensively in pulping industry, while lignin has been considered waste and is burned to generate heat. Lignin, a complex aromatic polymer component of biomass, has the potential to be used as a source of aromatic chemicals and pharmaceutical synthons. The recalcitrant nature of lignin, the lack of effective lignin breakdown methods and analytical techniques to analyze it are …

Synthesis And Characterization Of D5-Barbarin For Use In Barbarin-Related Research, Sucheta Kudrimoti, Jacob Machin, Adedamola S. Arojojoye, Samuel G. Awuah, Rodney Eisenberg, Clara Fenger, George Maylin, Andreas F. Lehner, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d₅-barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D₅-barbarin synthesis commenced with production of d₅-2-oxo-2-phenylacetaldehyde oxime (d₅-oxime) from d₅-acetophenone via butylnitrite in an ethoxide/ethanol solution. This d₅-oxime was then reduced with lithium aluminum …

Characteristics And Assessing Biological Risks Of Airborne Bacteria In Waste Sorting Plant, Abbas Norouzian Baghani, Somayeh Golbaz, Gholamreza Ebrahimzadeh, Marcelo I. Guzman, Mahdieh Delikhoon, Mehdi Jamshidi Rastani, Abdullah Barkhordari, Ramin Nabizadeh

Chemistry Faculty Publications

Examining the concentration and types of airborne bacteria in waste paper and cardboard sorting plants (WPCSP) is an urgent matter to inform policy makers about the health impacts on exposed workers. Herein, we collected 20 samples at 9 points of a WPCSP every 6 winter days, and found that the most abundant airborne bacteria were positively and negatively correlated to relative humidity and temperature, respectively. The most abundant airborne bacteria (in units of CFU m⁻³) were: Staphylococcus sp. (72.4) > Micrococcus sp. (52.2) > Bacillus sp. (30.3) > Enterococcus sp. (24.0) > Serratia marcescens (20.1) > E. coli (19.1) > Pseudomonas sp. (16.0) > Nocardia …

Investigating The Physical Stability Of Amorphous Pharmaceutical Formulations, Travis W. Jarrells

Theses and Dissertations--Pharmacy

Amorphous formulations, including amorphous solid dispersions (ASDs), consisting of the active pharmaceutical ingredient (API) intimately mixed in a polymeric matrix, are an attractive formulation approach to improve drug delivery, dissolution, and solubility. However, an amorphous API in an ASD is in a higher energy state compared to the crystalline drug and results in most ASDs being inherently unstable. The polymer helps to stabilize the amorphous drug against crystallization such that the resulting homogenous mixture maintains its solubility advantage relative to the crystalline form. One challenge of ASDs is that the presence of impurities including crystals or residual solvent, variations in …

A Study Of The Analysis Of Hemp-Derived Oil Products: Development Of A Method For The Analysis Of Phytocannabinoids In Medicinal Products, Erin Johnson

Theses and Dissertations--Pharmacology and Nutritional Sciences

Human interactions with cannabis have a history spanning millennia as a source of fiber, food, and medicine. The plant came across Asia, Europe, and Africa with the movements of people and travelers eventually coming to the Americas with European explorers. In colonizing North America, cannabis fiber was key to the production of canvas and ropes for ships. Although fiber was the driver for cannabis production in the United States, medicinal uses were prevalent and propelled the eventual regulations. The Pure Food and Drug Act of 1906 mandated accurate labeling on drugs such as cannabis followed by the Marihuana Tax Act …

Development Of Accurate And Efficient Computational Methodologies For Predicting Protein-Ligand And Protein-Protein Binding Free Energies, Alexander Hamilton Williams

Theses and Dissertations--Pharmacy

Computational modeling is an invaluable tool in the drug discovery process either for small ligand or protein therapeutics. The widespread availability of protein X-Ray Crystal and Cryo-Electron Microscopy (Cryo-EM) structures has allowed for more accurate molecular dynamics (MD) simulations that are not reliant on methods such as homology modeling, which may produce structures that require significant computational time to demonstrate their stability. In this thesis we describe several novel methodologies for the computationally efficient modeling of protein/ligand and protein/protein complexes that may be employed within both large-scale virtual screenings and lead compound optimization. These methodologies may also be utilized in …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Mansouramycins E–G, Cytotoxic Isoquinolinequinones From Marine Streptomycetes, Mohamed Shaaban, Khaled A. Shaaban, Gerhard Kelter, Heinz Herbert Fiebig, Hartmut Laatsch

Center for Pharmaceutical Research and Innovation Faculty Publications

Chemical investigation of the ethyl acetate extract from the marine-derived Streptomyces sp. isolate B1848 resulted in three new isoquinolinequinone derivatives, the mansouramycins E–G (1a–3a), in addition to the previously reported mansouramycins A (5) and D (6). Their structures were elucidated by computer-assisted interpretation of 1D and 2D NMR spectra, high-resolution mass spectrometry, and by comparison with related compounds. Cytotoxicity profiling of the mansouramycins in a panel of up to 36 tumor cell lines indicated a significant cytotoxicity and good tumor selectivity for mansouramycin F (2a), while the activity profile of E ( …

Aberrant Crosstalk Between Insulin Signaling And Mtor In Young Down Syndrome Individuals Revealed By Neuronal-Derived Extracellular Vesicles, Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone

Chemistry Faculty Publications

INTRODUCTION: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing.

METHODS: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways.

RESULTS: nEVs isolated from DS children were characterized by a significant increase in pIRS1^Ser636, a marker of …

Biotinylation As A Tool To Enhance The Uptake Of Small Molecules In Gram-Negative Bacteria, Ankit Pandeya, Ling Yang, Olaniyi Alegun, Chamikara Karunasena, Chad Risko, Zhenyu Li, Yinan Wei

Chemistry Faculty Publications

Antibiotic resistance is a major public health concern. The shrinking selection of effective antibiotics and lack of new development is making the situation worse. Gram-negative bacteria more specifically pose serious threat because of their double layered cell envelope and effective efflux systems, which is a challenge for drugs to penetrate. One promising approach to breach this barrier is the “Trojan horse strategy”. In this technique, an antibiotic molecule is conjugated with a nutrient molecule that helps the antibiotic to enter the cell through dedicated transporters for the nutrient. Here, we explored the approach using biotin conjugation with a florescent molecule …

Metal-Free Domino Amination-Knoevenagel Condensation Approach To Access New Coumarins As Potent Nanomolar Inhibitors Of Vegfr-2 And Egfr, Essam M. Eliwa, Marcel Frese, Ahmed H. Halawa, Maha M. Soltan, Larissa V. Ponomareva, Jon S. Thorson, Khaled A. Shaaban, Mohamed Shaaban, Ahmed M. El-Agrody, Norbert Sewald

Center for Pharmaceutical Research and Innovation Faculty Publications

A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC₅₀ values of 15.5 ± 3.54 …

Neuron-Derived Extracellular Vesicles Modulate Microglia Activation And Function, Hui Peng, Brock T. Harvey, Christopher I. Richards, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Microglia act as the immune cells of the central nervous system (CNS). They play an important role in maintaining brain homeostasis but also in mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for neuroimmune regulation and subsequent effects on CNS integrity. However, the molecular mechanisms of neuron-glia communication in regulating microglia function are not fully understood. One recently described means of this intercellular communication is via nano-sized extracellular vesicles (EVs) that transfer a large diversity of molecules between neurons and microglia, such as proteins, lipids, and nucleic acids. To determine the effects of …

Modes Of Transmission Of Severe Acute Respiratory Syndrome-Coronavirus-2 (Sars-Cov-2) And Factors Influencing On The Airborne Transmission: A Review, Mahdieh Delikhoon, Marcelo I. Guzman, Ramin Nabizadeh, Abbas Norouzian Baghani

Chemistry Faculty Publications

The multiple modes of SARS-CoV-2 transmission including airborne, droplet, contact, and fecal–oral transmissions that cause coronavirus disease 2019 (COVID-19) contribute to a public threat to the lives of people worldwide. Herein, different databases are reviewed to evaluate modes of transmission of SARS-CoV-2 and study the effects of negative pressure ventilation, air conditioning system, and related protection approaches of this virus. Droplet transmission was commonly reported to occur in particles with diameter >5 µm that can quickly settle gravitationally on surfaces (1–2 m). Instead, fine and ultrafine particles (airborne transmission) can stay suspended for an extended period of time (≥2 h) …

Design, Synthesis, And Anticancer Properties Of Ru(Ii) Complexes With Organometallic, “Expanded” Bipyridine, And O,O’-Chelating Ligands, Raphael Ryan

Theses and Dissertations--Chemistry

Cancer is a worldwide public health crisis that requires new and improved drugs to be developed to extend survival rates and improve quality of life for the patient. Platinum-based drugs are used in approximately 50% of cancer treatment regimens. These drugs are highly effective in many kinds of cancer; however, cancers can develop platinum resistance and these drugs have troubling side effects that reduced their use and efficacy. To overcome these disadvantages, many other metals have been studied for their anticancer properties. Notably, the anticancer properties of ruthenium-based agents have drawn considerable attention with multiple ruthenium complexes entering clinical trials. …

An Overview Of The Effect Of Bioaerosol Size In Coronavirus Disease 2019 Transmission, Marcelo I. Guzman

Chemistry Faculty Publications

The fast spread of coronavirus disease 2019 (COVID-19) constitutes a worldwide challenge to the public health, educational and trade systems, affecting the overall well-being of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Such measures can reduce the exposure to bioaerosols, which can result in pathogen deposition in the respiratory tract of the host causing disease and an immunological response. Thus, it is important to consider the validity of the proposal for keeping a distance of …

Synthesis, Characterization, And Antiproliferative Activity Of Novel Chiral [Quinoxp*Aucl2]+ Complexes, Adedamola S. Arojojoye, R. Tyler Mertens, Samuel Ofori, Sean R. Parkin, Samuel G. Awuah

Chemistry Faculty Publications

Herein is reported the synthesis of two Au(III) complexes bearing the (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting two stoichiometric equivalents of HAuCl₄.3H₂O to one equivalent of the corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) were formed, respectively, in moderate yields. The structure of (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) was further confirmed by X-ray crystallography. The antiproliferative activities of the two compounds were evaluated in a panel of cell lines and exhibited promising results comparable to auranofin and cisplatin with …

Mitochondrial Oxidative And Nitrosative Stress And Alzheimer Disease, D. Allan Butterfield, Debra Boyd-Kimball

Chemistry Faculty Publications

Oxidative and nitrosative stress are widely recognized as critical factors in the pathogenesis and progression of Alzheimer disease (AD) and its earlier stage, amnestic mild cognitive impairment (MCI). A major source of free radicals that lead to oxidative and nitrosative damage is mitochondria. This review paper discusses oxidative and nitrosative stress and markers thereof in the brain, along with redox proteomics, which are techniques that have been pioneered in the Butterfield laboratory. Selected biological alterations in—and oxidative and nitrosative modifications of—mitochondria in AD and MCI and systems of relevance thereof also are presented. The review article concludes with a section …

The Bach1/Nrf2 Axis In Brain In Down Syndrome And Transition To Alzheimer Disease-Like Neuropathology And Dementia, Marzia Perluigi, Antonella Tramutola, Sara Pagnotta, Eugenio Barone, D. Allan Butterfield

Chemistry Faculty Publications

Down syndrome (DS) is the most common genetic cause of intellectual disability that is associated with an increased risk to develop early-onset Alzheimer-like dementia (AD). The brain neuropathological features include alteration of redox homeostasis, mitochondrial deficits, inflammation, accumulation of both amyloid beta-peptide oligomers and senile plaques, as well as aggregated hyperphosphorylated tau protein-containing neurofibrillary tangles, among others. It is worth mentioning that some of the triplicated genes encoded are likely to cause increased oxidative stress (OS) conditions that are also associated with reduced cellular responses. Published studies from our laboratories propose that increased oxidative damage occurs early in life in …

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO₂ nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …

Plasma And Serum Proteins Bound To Nanoceria: Insights Into Pathways By Which Nanoceria May Exert Its Beneficial And Deleterious Effects In Vivo, D. Allan Butterfield, Binghui Wang, Peng Wu, Sarita S. Hardas, Jason M. Unrine, Eric A. Grulke, Jian Cai, Jon B. Klein, William M. Pierce, Robert A. Yokel, Rukhsana Sultana

Chemistry Faculty Publications

Nanoceria (CeO2, cerium oxide nanoparticles) is proposed as a therapeutic for multiple disorders. In blood, nanoceria becomes protein-coated, changing its surface properties to yield a different presentation to cells. There is little information on the interaction of nanoceria with blood proteins. The current study is the first to report the proteomics identification of plasma and serum proteins adsorbed to nanoceria. The results identify a number of plasma and serum proteins interacting with nanoceria, proteins whose normal activities regulate numerous cell functions: antioxidant/detoxification, energy regulation, lipoproteins, signaling, complement, immune function, coagulation, iron homeostasis, proteolysis, inflammation, protein folding, protease inhibition, adhesion, protein/RNA …

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 …

Crystal Structure Of Zymonic Acid And A Redetermination Of Its Precursor, Pyruvic Acid, Dominik Heger, Alexis J. Eugene, Sean R. Parkin, Marcelo I. Guzman

Chemistry Faculty Publications

The structure of zymonic acid (systematic name: 4-hy­droxy-2-methyl-5-oxo-2,5-di­hydro­furan-2-carb­oxy­lic acid), C₆H₆O₅, which had previously eluded crystallographic determination, is presented here for the first time. It forms by intra­molecular condensation of parapyruvic acid, which is the product of aldol condensation of pyruvic acid. A redetermination of the crystal structure of pyruvic acid (systematic name: 2-oxo­propanoic acid), C₃H₄O₃, at low temperature (90 K) and with increased precision, is also presented [for the previous structure, see: Harata et al. (1977). Acta Cryst. B33, 210–212]. In zymonic acid, the hy­droxy­lactone ring …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

Toward An Enzyme-Coupled, Bioorthogonal Platform For Methyltransferases: Probing The Specificity Of Methionine Adenosyltransferases, Tyler D. Huber

Theses and Dissertations--Pharmacy

Methyl group transfer from S-adenosyl-l-methionine (AdoMet) to various substrates including DNA, proteins, and natural products (NPs), is accomplished by methyltransferases (MTs). Analogs of AdoMet, bearing an alternative S-alkyl group can be exploited, in the context of an array of wild-type MT-catalyzed reactions, to differentially alkylate DNA, proteins, and NPs. This technology provides a means to elucidate MT targets by the MT-mediated installation of chemoselective handles from AdoMet analogs to biologically relevant molecules and affords researchers a fresh route to diversify NP scaffolds by permitting the differential alkylation of chemical sites vulnerable to NP MTs that are unreactive to …

Canvass: A Crowd-Sourced, Natural-Product Screening Library For Exploring Biological Space, Sara E. Kearney, Gergely ZahoráNszky-KőHalmi, Kyle R. Brimacombe, Mark J. Henderson, Caitlin Lynch, Tongan Zhao, Kanny K. Wan, Zina Itkin, Christopher Dillon, Min Shen, Dorian M. Cheff, Tobie D. Lee, Danielle Bougie, Ken Cheng, Nathan P. Coussens, Dorjbal Dorjsuren, Richard T. Eastman, Ruili Huang, Michael J. Iannotti, Surendra Karavadhi, Carleen Klumpp-Thomas, Jacob S. Roth, Srilatha Sakamuru, Wei Sun, Steven A. Titus, Adam Yasgar, Ya-Qin Zhang, Jinghua Zhao, Rodrigo B. Andrade, M. Kevin Brown, Robert B. Grossman

Chemistry Faculty Publications

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The …

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …

Treatment Of Mci And Alzheimer's Disease, Mark A. Lovell, Bert C. Lynn

Chemistry Faculty Patents

The present invention provides, among other things, therapeutic compositions and methods that can effectively treat, slow or prevent a neurological disease (e.g., a neurodegenerative disease, e.g., mild cognitive impairment (MCI) or Alzheimer's disease (AD)), in particular, based on therapeutically effective amount of nifedipine, oxidized or nitroso nifedipine derivatives, lactam (e.g., a compound of formula (Ic) or (Ic-i), e.g., NFD-L1), thyroxine (T4), triiodothyronine (T3) and combinations thereof.

Solution Growth And Thermal Treatment Of Crystals Lead To Two New Forms Of 2-((2,6-Dimethylphenyl)Amino)Benzoic Acid, Rong Hu, Yunping Zhoujin, Meng Liu, Mingtao Zhang, Sean Parkin, Panpan Zhou, Jianzhi Wang, Faquan Yu, Sihui Long

Chemistry Faculty Publications

We report the discovery of two new forms (II and III) of a potential non-steroidal anti-inflammatory and thyroid drug, 2-((2,6-dimethylphenyl)amino)benzoic acid (HDMPA) through solution growth and thermal treatment of crystals. Form II has been discovered through crystal growth in a variety of solvents, and characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), FT-IR, and Raman spectroscopy. Form II converts into form III upon thermal treatment, as indicated by the phase behavior study of form II with differential scanning calorimetry (DSC). Form III has been characterized by IR, Raman and PXRD. Conformational flexibility of the molecule seems to lead to …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …