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Articles 31 - 60 of 61

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres Jan 2014

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of ...


Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago Jan 2014

Dj-1 And Atp13a2: Two Proteins Involved In Parkinson’S Disease, Josephat M Asiago

Open Access Dissertations

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 0.3% of the total U.S. population, and its prevalence increases with age. Two neuropathological hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta, a region in the midbrain involved in initiating and sustaining movement, and the presence of cytosolic inclusions called Lewy bodies (LBs) in various brain regions. LBs are enriched with fibrillar forms of the presynaptic protein &agr;-synuclein (aSyn). Two autosomal recessive genes implicated in familial PD are PARK9, encoding the P-type ATPase ATP13A2 ...


Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans Nov 2011

Promise Of Advances In Simulation Methods For Protein Crystallography: Implicit Solvent Models, Time-Averaging Refinement, And Quantum Mechanical Modeling, Celia Schiffer, Jan Hermans

Celia A. Schiffer

No abstract provided.


Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin Nov 2011

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational ...


Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer Nov 2011

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an ...


Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom Nov 2011

Viral Protease Inhibitors, Jeffrey Anderson, Celia Schiffer, Sook-Kyung Lee, Ronald Swanstrom

Celia A. Schiffer

This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses ...


Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer Nov 2011

Mutation Patterns And Structural Correlates In Human Immunodeficiency Virus Type 1 Protease Following Different Protease Inhibitor Treatments, Thomas Wu, Celia Schiffer, Matthew Gonzales, Jonathan Taylor, Rami Kantor, Sunwen Chou, Dennis Israelski, Andrew Zolopa, W. Jeffrey Fessel, Robert Shafer

Celia A. Schiffer

Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or in succession, mutation patterns of protease isolates from these persons have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 isolates from 1,919 persons with different protease inhibitor experiences: 1,004 isolates from untreated persons, 637 isolates from persons who received one protease inhibitor, and 603 isolates from persons receiving two or more protease inhibitors. The median number of protease mutations per isolate increased from 4 in untreated persons to 12 in persons who had received four ...


Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer Nov 2011

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from ...


Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren Nov 2011

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in ...


Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer Nov 2011

Resilience To Resistance Of Hiv-1 Protease Inhibitors: Profile Of Darunavir, Eric Lefebvre, Celia A. Schiffer

Celia A. Schiffer

The current effectiveness of HAART in the management of HIV infection is compromised by the emergence of extensively cross-resistant strains of HIV-1, requiring a significant need for new therapeutic agents. Due to its crucial role in viral maturation and therefore HIV-1 replication and infectivity, the HIV-1 protease continues to be a major development target for antiretroviral therapy. However, new protease inhibitors must have higher thresholds to the development of resistance and cross-resistance. Research has demonstrated that the binding characteristics between a protease inhibitor and the active site of the HIV-1 protease are key factors in the development of resistance. More ...


Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer Nov 2011

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.


Investigation Of Protein Unfolding And Stability By Computer Simulation, Wilfred Van Gunsteren, P. Hunenberger, H. Kovacs, A. Mark, Celia Schiffer Nov 2011

Investigation Of Protein Unfolding And Stability By Computer Simulation, Wilfred Van Gunsteren, P. Hunenberger, H. Kovacs, A. Mark, Celia Schiffer

Celia A. Schiffer

Structural, dynamic and energetic properties of proteins in solution can be studied in atomic detail by molecular dynamics computer simulation. Protein unfolding can be caused by a variety of driving forces induced in different ways: increased temperature or pressure, change of solvent composition, or protein amino acid mutation. The stability and unfolding of four different proteins (bovine pancreatic trypsin inhibitor, hen egg white lysozyme, the surfactant protein C and the DNA-binding domain of the 434 repressor) have been studied by applying the afore-mentioned driving forces and also to some artificial forces. The results give a picture of protein (in)stability ...


Apoptotic And Chemotherapeutic Properties Of Iron (Iii)-Salophene In An Ovarian Cancer Animal Model, Thilo S. Lange, Carolyn Mccourt, Rakesh K. Singh, Kyu Kwang Kim, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard Sep 2009

Apoptotic And Chemotherapeutic Properties Of Iron (Iii)-Salophene In An Ovarian Cancer Animal Model, Thilo S. Lange, Carolyn Mccourt, Rakesh K. Singh, Kyu Kwang Kim, Ajay P. Singh, Brian S. Luisi, Onur Alptürk, Robert M. Strongin, Laurent Brard

Chemistry Faculty Publications and Presentations

The cytotoxicity of organometallic compounds iron(III)-, cobalt(III)-, manganese(II)-, and copper(II)-salophene (-SP) on platinum-resistant ovarian cancer cell lines was compared. Fe-SP displayed selective cytotoxicity (IC(50) at ~1 muM) against SKOV-3 and OVCAR-3 cell lines while Co-SP caused cytotoxic effects only at higher concentrations (IC(50) at 60 muM) and Cu-SP effects were negligible. High cytotoxicity of Mn-SP (30-60 muM) appeared to be nonspecific because the Mn-chloride salt reduced cell viability similarly. The effect of Fe-SP at 1 muM proved to be ovarian cancer cell selective when compared to a panel of cell lines derived from ...


Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard May 2008

Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard

Chemistry Faculty Publications and Presentations

Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovariancancer cell lines were investigated.

Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented ...


Mesoporous Silica Nanomaterials And Magnetic Nanoparticles Based Stimuli-Responsive Controlled-Release Delivery Systems, Supratim Giri Jan 2008

Mesoporous Silica Nanomaterials And Magnetic Nanoparticles Based Stimuli-Responsive Controlled-Release Delivery Systems, Supratim Giri

Retrospective Theses and Dissertations

The research presented and discussed within this dissertation involves the development of mesoporous silica nanomaterials and magnetic nanoparticles based stimuli-responsive controlled-release delivery systems.;A superparamagnetic iron oxide nanoparticle-capped, MCM-41 type mesoporous silica nanorod-based controlled-release delivery system (Magnet-MSN) was synthesized. The stimuli-responsive release profiles of fluorescein-loaded Magnet-MSN delivery systems in the presence of external magnetic field was studied by using cell-produced antioxidants as triggers for releasing fluorescein molecules. The intracellular delivery efficiency of the Magnet-MSN system with human cervical cancer cells (HeLa) in vitro was demonstrated involving fluorescein molecules as model drug.;To take the advantage of the intracellular delivery capability ...


Synthesis Of Natural Compounds In Echinacea , Jaehoon Bae Jan 2006

Synthesis Of Natural Compounds In Echinacea , Jaehoon Bae

Retrospective Theses and Dissertations

In this dissertation, we have investigated the direct and efficient synthetic route to biologically active natural products. Chapter 1 describes the synthesis of some of the natural compounds in Echinacea. Several main constituents of the plant Echinacea have been synthesized for the first time. We have developed a direct and flexible route to amides and ketones in Echinacea. The synthesized natural products have been used for standard samples for the biological studies. Chapter 2 describes the new tandem strategy to construct bicyclic systems by a Diels-Alder/ene reaction and its application for the synthesis of Isoligularone. During this tandem reaction ...


Enantiomeric Chromatographic Separations And Ionic Liquids , Jie Ding Jan 2005

Enantiomeric Chromatographic Separations And Ionic Liquids , Jie Ding

Retrospective Theses and Dissertations

The chiral nature of compounds contributes to their bioactivity and their various pharmaceutical/industrial uses. As a result, the Food and Drug Administration (FDA) has implemented policies for analyzing the enantiomers of chiral compounds. Gas chromatography (GC) and liquid chromatography (LC) utilizing chiral stationary phases are the two most commonly used methods to achieve direct enantiomeric separations of chiral compounds. The first part of this dissertation includes a review of direct separation of enantiomers in gas and liquid chromatography, an example of the enantiomeric separation of various racemic sulfoxides and sulfinate esters on four derivatized cyclodextrin chiral stationary phases using ...


New Palladium-Catalyzed Approaches To Heterocycles And Carbocycles, Qinhua Huang Jan 2004

New Palladium-Catalyzed Approaches To Heterocycles And Carbocycles, Qinhua Huang

Retrospective Theses and Dissertations

The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I2, ICl, PhSeCl, PhSCl and p-O2NC6H4SCl to give the corresponding halogen-, selenium- and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields.;The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines ...


Synthesis Of Polycyclic Natural Products , Tuan Hoang Nguyen Jan 2003

Synthesis Of Polycyclic Natural Products , Tuan Hoang Nguyen

Retrospective Theses and Dissertations

Highly oxidized polycyclic natural products are abundant in nature and have diverse biological activities. Hyperforin has been identified as the sole constituent responsible for the antidepressant characteristic of St. John's wort. An approach to an oxidized bicyclic phloroglucin core of hyperforin is described. Puupehenone, a sesquiterpene found in marine sponges, has recently emerged as a strong candidate to treat tuberculosis. The synthesis of the BCD rings of puupehenone containing a quinone methide moiety is described.


New Methods For The Synthesis Of Natural Products , Alexey G. Melekhov Jan 1999

New Methods For The Synthesis Of Natural Products , Alexey G. Melekhov

Retrospective Theses and Dissertations

In this work we developed new approaches to three different classes of compounds. In the first chapter we employed PIFA as an oxidant to develop a direct route to pyrrolobenzodiazepines. We also developed a new way to generate acyl radicals by oxidative decarboxylation. The utility of this methodology was shown in the synthesis of 8-deoxy DC-81. In the second chapter we developed a five-step synthetic route to 1,4-phenanthrenequinones. We also used one of these phenanthrenequinones for the construction of an angularly-fused aromatic systems. In the third chapter we studied Lewis acid-mediated cyclizations of acyl quinones. We synthesized a precursor ...


Combination Of Capillary Isoelectric Focusing And Liquid Chromatography With Electrospray Ionization Mass Spectrometry For Protein Characterization , Jing Wei Jan 1998

Combination Of Capillary Isoelectric Focusing And Liquid Chromatography With Electrospray Ionization Mass Spectrometry For Protein Characterization , Jing Wei

Retrospective Theses and Dissertations

Combination of capillary isoelectric focusing (CIEF) and liquid chromatography (LC) with electrospray ionization mass spectrometry (ESIMS) is utilized for protein characterization;Both CIEF-ESIMS and LC-MS are studied for phosphoprotein characterization. At the intact protein level, on-line CTEF-ESIMS is applied for phosphorylation analysis to obtain the two dimensional information: isoelectric point and molecular mass. At the peptide level, on-line LC-ESI-MS and LC-ESI neutral loss MS/MS were highly specific for the determination of sites of phosphorylation and successfully applied on the tryptic digest of tau proteins phosphorylated by different kinases;On-line combination of CIEF with ESI-TOF MS is demonstrated for high ...


Capillary Electrophoresis Separation Of Neutral Organic Compounds, Pharmaceutical Drugs, Proteins And Peptides, Enantiomers And Anions , Wei-Liang Ding Jan 1998

Capillary Electrophoresis Separation Of Neutral Organic Compounds, Pharmaceutical Drugs, Proteins And Peptides, Enantiomers And Anions , Wei-Liang Ding

Retrospective Theses and Dissertations

Addition of a novel anionic surfactant, namely lauryl polyoxyethylene sulfate, to an aqueous-acetonitrile electrolyte makes it possible to separate nonionic organic compounds by capillary electrophoresis. Separation is based on differences in the association between analytes and the surfactant. Highly hydrophobic compounds such as polyaromatic hydrocarbons are well separated by this new surfactant. Migration times of analytes can be readily changed over an unusually large range by varying the additive concentration and the proportion of acetonitrile in the electrolyte. Several examples are given, including the separation of four methylbenz (a) anthracene isomers and the separation of normal and deuterated acetophenone;The ...


Novel Materials And Methods For Solid-Phase Extraction And High-Performance Liquid Chromatography , Dianna Lynn Ambrose Jan 1997

Novel Materials And Methods For Solid-Phase Extraction And High-Performance Liquid Chromatography , Dianna Lynn Ambrose

Retrospective Theses and Dissertations

Solid-phase extraction (SPE) is one of the most popular sample preparation techniques for the isolation and preconcentration of organic compounds from aqueous samples. Modified porous polystyrene-divinylbenzene (PS-DVB) resins containing polar groups are superior for SPE of organic solutes from aqueous samples. These modified resins display excellent surface hydrophilicity and improved extraction efficiencies. Silicalite is a hydrophobic molecular sieve with an unusual crystal structure. Because of its unique structure, Silicalite adsorbs organic analytes from aqueous samples due to hydrophobic interactions;The ability of Silicalite and a lightly sulfonated PS-DVB resin to extract various organic test compounds from aqueous samples was compared ...


Electrochemically-Modulated Liquid Chromatography (Emlc): Column Design, Retention Processes, And Applications , En-Yi Ting Jan 1997

Electrochemically-Modulated Liquid Chromatography (Emlc): Column Design, Retention Processes, And Applications , En-Yi Ting

Retrospective Theses and Dissertations

This dissertation explores a new separation technique, electrochemically modulated liquid chromatography (EMLC), from the column design, retention processes, to the pharmaceutical applications. A literature review, general summary, and perspectives of this technique are also described. Chapter 1 presents the newly designed EMLC column. The principal modification of this design is to connect the porous stainless steel column as counter electrode as opposed to part of working electrode in the previous design. The improvement in performance from this modification results in a shorter response time to changes in applied potential (E appl) and a better control of E appl at cathodic ...


Total Synthesis Of Angularly Fused Natural Products , Guohua Zhao Jan 1996

Total Synthesis Of Angularly Fused Natural Products , Guohua Zhao

Retrospective Theses and Dissertations

The synthesis of angularly fused quinone natural product G-2N has been achieved using a photoenolization reaction and a Diels-Alder reaction in the key carbon-carbon bond forming steps. This route is direct and flexible. It should be applicable to synthesis of other analogous natural products;The skeleton of colchicine has been achieved using a Diels-Alder reaction followed by an electrophilic addition to the A ring as key steps. Our synthetic approach is direct. It could provide an efficient entry to total synthesis of colchicine.


Synthesis Of Diterpene Alkaloids , Tiberiu Mircea Siclovan Jan 1996

Synthesis Of Diterpene Alkaloids , Tiberiu Mircea Siclovan

Retrospective Theses and Dissertations

Aconitine, atisine and garrya type diterpene alkaloids show remarkable biological activity and have a number of structural features in common. Due to their complex structure, there is a discrepancy between progress made lately in the identification, isolation and characterization of new members of this family, on one hand, and successful efforts towards their total synthesis, on the other;Our synthetic studies led us to develop a highly reproducible synthesis of adamantane-containing compounds via the corresponding bridgehead anions;Studies on the application of functionalized bridgehead radicals in natural product synthesis resulted in the development of a versatile, mild and highly tolerant ...


Synthetic Approaches To Huperzine A , Danette René Vines Jan 1994

Synthetic Approaches To Huperzine A , Danette René Vines

Retrospective Theses and Dissertations

The natural product huperzine A has been found to possess activity as a nootropic agent. Because of its memory facilitating effects, huperzine A represents a promising drug for the treatment of neurodegenerative diseases, such as Alzheimer's disease. As life expectancy increases, identifying and synthesizing drugs which treat cognitive dysfunction becomes a primary health objective;This study was undertaken to synthesize huperzine A, and to offer a direct route to improved analogs of huperzine A. A bicyclic amino ketone for the synthesis of huperzine A was prepared in six steps. The conjugate addition of metallated alkylpyridines afforded a direct route ...


Synthesis, Structure Features And Application Of Pro-Azaphsphatranes As Catalysts And Strong Non-Ionic Bases In Organic Synthesis , Jiansheng Tang Jan 1994

Synthesis, Structure Features And Application Of Pro-Azaphsphatranes As Catalysts And Strong Non-Ionic Bases In Organic Synthesis , Jiansheng Tang

Retrospective Theses and Dissertations

This dissertation describes the development of pro-azaphosphatranes ZP(MeNCH[subscript]2CH[subscript]2)[subscript]3N as versatile useful materials in organic synthesis;Pro-imidophosphatranes MeN= P(MeNCH[subscript]2CH[subscript]2)[subscript]3N and PhN= P(MeNCH[subscript]2CH[subscript]2)[subscript]3N, their corresponding acyclic analogues MeN= P(NMe[subscript]2)[subscript]3 and PhN= P(NMe[subscript]2)[subscript]3, and their conjugate acids as well as the conjugate acid of the commercially available non-ionic base P[subscript]4-t-Bu (i.e. t-BuN=P (N=P(NMe[subscript]2)[subscript]3][subscript]3) have been synthesized. Equilibria measured by [superscript ...


Development Of An Ocular Drug Release System For Cattle , Thomas Quang Dinh Jan 1991

Development Of An Ocular Drug Release System For Cattle , Thomas Quang Dinh

Retrospective Theses and Dissertations

An erodible ring-shaped ocular insert containing an antibiotic (tylosin tartrate) has been developed for treatment of infectious bovine keratoconjunctivitis (IBK). Four additional tasks have been completed: (1) a test to determine the retention time of the ocular device in the eyes of the calves, (2) an in vitro test to determine the degradation characteristics of the device, (3) an in vitro study to obtain the drug release profiles of the insert, and (4) a study to compare the use of rings and a field treatment method using infected cattle;The device remained in the eyes an average of 3.92 ...


Synthetic Dibenzofurans Structurally Related To Known Analgesics, Frederick Albert Yeoman Jan 1944

Synthetic Dibenzofurans Structurally Related To Known Analgesics, Frederick Albert Yeoman

Retrospective Theses and Dissertations

No abstract provided.