Medicinal-Pharmaceutical Chemistry Commons^™

Studies On The Synthesis Of Orthogonally Protected Azalanthionines, And Of Routes Towards B-Methyl Azalanthionines, By Ring-Opening Of N-Activated Aziridine-2-Crboxylates, Keith O'Brien, Keith Ó Proinsias, Fintan Kelleher

Articles

Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding b-methyl azalanthionines have, so far, been unsuccessful.

Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina

Seton Hall University Dissertations and Theses (ETDs)

The cancer epidemic continues to afflict millions of humans world-wide each year and despite a renewed hope with the development of new and improved forms of therapy, a cure for cancer remains an elusive goal. This is partly related to the rise of resilient forms of tumors that have evolved with resistance towards conventional chemotherapy and radiation treatments. Moreover, these non-specific therapeutic regimens are highly toxic, leading to severe immunosuppressive effects which poisons the body and compromises the road towards remission. In an effort to mitigate these limitations, cancer-targeting approaches are currently experiencing a renaissance in the translation of new …

Cu (Ii) Catalyzed Gateways In The Synthesis Of Acridine Derivatives And Their Biological Evaluation As Anti-Cancer Drugs, Rajesh Komati

LSU New Orleans Theses and Dissertations

Telomeres are nucleoprotein complexes found at the ends of linear eukaryotic chromosomes. Telomeres consist of a short sequence of repetitive double stranded DNA, TTAGGG repeats in humans (and all mammals), and a complex of 6 proteins, termed the shelterin complex. The length of the telomeres varies greatly between species, from approximately 300 base pairs in yeast to many 10-15 kilo bases in humans, because of the end replication problem this length get shorten with each cell division and ultimately leads to cell death. However the immortal eukaryotic cells and some transformed human cells over come this incomplete end replication problem …

Design, Synthesis And Biological Evaluation Of Novel Compounds With Cns-Activity Targeting Cannabinoid And Biogenic Amine Receptors, Alexander M. Sherwood

LSU New Orleans Theses and Dissertations

This work seeks to contribute to the discipline of neuropharmacology by way of structure activity relationship from the standpoint of an organic chemist. More specifically, we sought to develop robust synthetic methodology able to efficiently produce an array of compounds for the purpose of systematic evaluation of their interaction with specific sights within the central nervous system (CNS) in order to better understand the mind and to develop drugs that may have beneficial effects on neurological function.

The focus of these studies has been toward the development of novel molecules, using a structure-activity relationship approach, that exhibit binding affinity at …

Green's Functions Of Discrete Fractional Calculus Boundary Value Problems And An Application Of Discrete Fractional Calculus To A Pharmacokinetic Model, Sutthirut Charoenphon

Masters Theses & Specialist Projects

Fractional calculus has been used as a research tool in the fields of pharmacology, biology, chemistry, and other areas [3]. The main purpose of this thesis is to calculate Green's functions of fractional difference equations, and to model problems in pharmacokinetics. We claim that the discrete fractional calculus yields the best prediction performance compared to the continuous fractional calculus in the application of a one-compartmental model of drug concentration. In Chapter 1, the Gamma function and its properties are discussed to establish a theoretical basis. Additionally, the basics of discrete fractional calculus are discussed using particular examples for further calculations. …

Functionalization And Modification Of Naphthaquinone Analogs As Her2 Kinase Inhibitors, Divya Jyothi Lella

Masters Theses & Specialist Projects

HER2 overexpression in breast cancer tumors predicts lower overall survival. Because of the aggressive nature of HER2 tumors and the association with metastatic disease, the HER2 receptor holds great promise as a therapeutic target in metastatic breast cancer. We are developing small molecule inhibitors that bind to the ATP binding site of the tyrosine kinase domain in order to inhibit tyrosine auto-phosphorylation. This process controls biological pathways that mediate the cell growth. In normal cells this process is highly controlled. We are targeting the modification of the side chain of the hydroxy methyl group of 2-Hydroxy methyl-5,8-dimethoxy-1,4-naphthaquinone. These compounds should …

Selective Oxidations By Metalloporphyrins And Metallocorroles, Tse-Hong Chen

Masters Theses & Specialist Projects

Highly reactive transition metal-oxo intermediates are important active oxidant involved in numerous enzymes such as cytochrome P450 monooxygenases as well as in many useful metal-catalyzed oxidations. Many transition metal catalysts are designed for biomimetic studies of the predominant oxidation catalysts in Nature, the cytochrome P450 enzymes. In this work, a series of metalloporphyrin and metallocorrole complexes have been successfully synthesized and spectroscopically characterized by UV-vis, GCMS and ¹H-NMR. The utilization of these complexes as catalysts for selective oxidation of sulfides and photocatalytic aerobic oxidations of activated hydrocarbons were investigated. Ruthenium(II) porphyrin complexes (2) and iron(III) corrole complexes (4) with …

Radiopharmaceuticals: The Application Of Technetium-99m And Rhenium Complexes, Angela Kristin Binion

Renée Crown University Honors Thesis Projects - All

Nuclear imaging used in diagnostic medicine requires the use of radiopharmaceuticals to make biological areas visible under a gamma camera. Although much success has been found in the use of technetium based imaging agents, their corresponding rhenium complexes can provide insight into the chemical properties of these radiopharmaceuticals without the potentially damaging effects of radiation. Technetium and rhenium complexes utilize a bifunctional chelator to act as a linker between biological vectors and the metal, improving the coordination between the two. Ligands containing thiazole rings have been successfully coordinated to technetium or rhenium tricarbonyl complexes, although it is uncertain whether coordination …

Drug Screening Target For Alzheimer's Disease And Method Of Screening Potential Drugs, Joseph Audie, Sergei Y. Ponomarev

Chemistry & Physics Faculty Publications

Drug screening targets and method of screening for potential drugs for treatment or amelioration of Alzheimer's Disease are provided.

Metal Stopping Reagents Facilitate Discontinuous Activity Assays Of The De Novo Purine Biosynthesis Enzyme Pure, Kelly L. Sullivan, Loredana C. Huma, Elwood Mullins, Michael E. Johnson, T. Joseph Kappock

Department of Biochemistry Faculty Publications

The conversion of 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynthesis: microbes and nonmetazoan eukaryotes use class I PurEs while animals use class II PurEs. Class I PurEs are therefore a potential antimicrobial target; however, no enzyme activity assay is suitable for high throughput screening (HTS). Here we report a simple chemical quench that fixes the PurE substrate/product ratio for 24 h, as assessed by the Bratton-Marshall assay (BMA) for diazotizable amines. The ZnSO₄ stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile product by BMA or other HTS methods

Identification Of Tetrapeptides From A Mixture Based Positional Scanning Library That Can Restore Nm Full Agonist Function Of The L106p, I69t, I102s, A219v, C271y, And C271r Human Melanocortin-4 Polymorphic Receptors (Hmc4rs), Erica M. Haslach, Huisuo Huang, Marvin Dirain, Ginamarie Debevec, Phaedra Geer, Radleigh Santos, Marc Giulianotti, Clemencia Pinilla, Jon R. Appel, Skye R. Doering, Michael A. Walters, Richard A. Houghten, Carrie Haskell-Luevano

Mathematics Faculty Articles

Human obesity has been linked to genetic factors and single nucleotide polymorphisms (SNPs). Melanocortin-4 receptor (MC4R) SNPs have been associated with up to 6% frequency in morbidly obese children and adults. A potential therapy for individuals possessing such genetic modifications is the identification of molecules that can restore proper receptor signaling and function. These compounds could serve as personalized medications improving quality of life issues as well as alleviating diseases symptoms associated with obesity including type 2 diabetes. Several hMC4 SNP receptors have been pharmacologically characterized in vitro to have a decreased, or a lack of response, to endogenous agonists …

Expression And Characterization Of The Novel Oxidase Virh-Ox, John Dronzek

Chemistry Honors Papers

No abstract provided.

Structural Dynamics Of A Single-Stranded Rna–Helix Junction Using Nmr, Catherine D. Eichhorn, Hashim M. Al-Hashimi

Department of Chemistry: Faculty Publications

Many regulatory RNAs contain long single strands (ssRNA) that adjoin secondary structural elements. Here, we use NMR spectroscopy to study the dynamic properties of a 12-nucleotide (nt) ssRNA tail derived from the prequeuosine riboswitch linked to the 3′ end of a 48-nt hairpin. Analysis of chemical shifts, NOE connectivity, ¹³C spin relaxation, and residual dipolar coupling data suggests that the first two residues (A25 and U26) in the ssRNA tail stack onto the adjacent helix and assume an ordered conformation. The following U26-A27 step marks the beginning of an A₆-tract and forms an acute pivot point for …

Electrodeposition And Characterisation Of Copolymers Based On Pyrrole And 3,4-Ethylenedioxythiophene In Bmim Bf4 Using A Microcell Configuration, Lavinia Astratine, Edmond Magner, John Cassidy, Tony Betts

Articles

Electrochemical copolymerization of pyrrole (Py) and 3,4-ethylenedioxythiophene (EDOT) was performed in an ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate, (BMIM BF4) employing a ‘micro-cell’ in order to use the materials efficiently. Characterization of the copolymers formed on an ITO substrate was performed for different Py: EDOT ratios (1:2, 1:1, 2:1) in both aqueous and ionic liquid electrolytes. Electrochemical and spectroelectrochemical analysis revealed that the properties of the copolymer depend upon the Py/EDOT monomer ratio used. The copolymer PPy-co-PEDOT (2:1) displayed good stability, a switching time of 20 s and a colouration efficiency of 101.3 C-1cm2. The presence of Py in the copolymer stabilised …

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, a lysosomal ATPase; and …

Injectable Versus Inhalational Anesthesia In Veterinary Medicine, Samantha D. Christ

Natural Sciences Student Research Presentations

Is the better, safer choice in small animal surgery injectible or inhalational anesthsesia? This poster outlines the advantages and disadvantages of the two, with a focus on two widely-used anesthetics, Ketamine and Isoflurane. This project is from the Natural Science Poster Session at Parkland College

Periactin, Sarah A. Johnson

Natural Sciences Student Research Presentations

Poster examines the chemical makeup of Periactin, generic name Cyproheptadine Hydrocholoride. Classified as an antihistamine or antipruritic, the labeled uses for Periactin are for symptomatic relief of various allergic conditions. Periactin can also be used for the following unlabeled uses: Cushing's disease, carcinoid syndrome, vascular headaches, and as an appetite stimulant.

Focalin Xr: Dexmethylphenidate Hydrochloride, Andrea L. Sullivan

Natural Sciences Student Research Presentations

This poster presented at the Natural Sciences Poster Session features the cerebral stimulant Focalin XR, or Dexmethylphenidate Hydrochloride. It identifies names and uses, and illustrates its chemical makeup.

Gertrude B. Elion, Kelli N. Brost

Natural Sciences Student Research Presentations

This poster for the Natural Sciences Poster Session at Parkland College describes the accomplishments of Gertrude B. Elion, a biochemist and pharmacologist. Elion developed multiple anticancer, antivirals, and autoimmune drugs.

Leukeran, Leslie R. Hunt

Natural Sciences Student Research Presentations

Leukeran (generic name Chlorambucil) is used alone or with other antineoplastics to treat chronic lymphocytic leukemia, malignant lymphomas, Hodgkin's disease, giant follicular lymphoma, and cancers of the ovaries, breast, and testes. Unlabled uses include treatment of nonneoplastic conditions such as vasculitis complicating rheumatoid arthritis, autoimmune hemolytic anemias associated with cold agglutinins, lupus glomerulonephritis, idiopathic nephrotic syndrome, polycythenmia vera, and macroglobulinemia.