Polycyclic Compounds Commons^™

Effects Of Waterborne Benzo[A]Pyrene Embryonic Exposure On Development, Behavior, Reproduction, And Mitochondrial Bioenergetics In Zebrafish, Megha Patel

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen leading to adverse effects in the development of both humans and animals. BaP is also continuously present in the environment leading to regular exposure via inhalation or ingestion. Because organisms’ early life stages can be more susceptible to contaminant exposure, our focus was on BaP’s adverse impacts on survival, length, weight, behavior, bioenergetic state, and fecundity following developmental exposures. To study BaP’s impacts, zebrafish (Danio rerio) were used as a model organism. BaP is a ligand for the aryl hydrocarbon receptor (AHR in humans; Ahr in …

Digoxin Toxicity And Acute Renal Failure In A 75 Year-Old Female, Daniel Zaayenga, Andrew Caravello, Nicholas Tomasello

Stratford Campus Research Day

Digoxin toxicity can present with varying manifestations. While pathognomonic symptoms such as xanthopsia (object appearing yellow) are a board favorite it is not a required finding and is in fact not seen with most patients. Rather digoxin toxicity presents with more non-specific symptoms such as GI distress (anorexia, N/V) neurological distress (lethargy, fatigue, delirium, confusion, disorientation, weakness. EKG findings are varied and include premature ventricular contractions, bradycardia, atrial tachyarrhythmias with AV block, ventricular bigeminy, junctional rhythms, various degrees of AV nodal blockade, ventricular tachycardia, and ventricular fibrillation. Although rarely seen, digoxin is one of the only causes of bidirectional ventricular …

Synthesis Of Selenotryptophan For Protein Elucidation, James P. Reiselman

Belmont University Research Symposium (BURS)

Through complex intermolecular and intramolecular forces, proteins conformationally change to form complex 3-d geometry that carries out biochemical processes and mapping their structures is becoming a field of interest in the biological community. Techniques for modeling protein’s structure typically follow the path of X-ray crystallography, which has an intrinsic phase problem that can make reading the electron density map they produce very difficult. This can be mitigated by appending a heavy-atom containing amino acid analogue into a crystal sample of the protein being studied. A selenium containing tryptophan analogue will be synthesized to be appended into proteins as a chemical …

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Analysis Of Multigenerational Behavioral Effects Of Dietary Benzo[A]Pyrene Exposure In Adult Zebrafish, Mary Beth Gillespie

Honors Theses

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon that is linked to negative reproductive and developmental effects in humans and animals. Because BaP is carcinogenic, and its continued presence in the environment allows it to be inhaled and ingested, better understanding of the effects of BaP is needed. To determine the behavioral effects of BaP exposure, zebrafish were used as a model. Wild-type zebrafish (5D) underwent two separate 21-day dietary exposures to 2.5 and 25 μg BaP/g fish to compare how BaP exposure affects locomotor activity. Following the dietary exposure, fish were mated to obtain and raise the F1 generation to …

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 …

Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks

Honors Theses

Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I concluded …

Letter: When Less Is More: Dexamethasone Dosing For Brain Tumors, Minesh Mehta

Minesh Mehta

No abstract provided.

Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, Hari K. Akula

Dissertations, Theses, and Capstone Projects

The C4 amide carbonyl of O-t-butyldimethylsilyl-protected thymidine, 2’-deoxyuridine, and 3’-azidothymidine (AZT) was activated by reaction with (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF as solvent. This led to the formation of corresponding O⁴-(benzotriazol-1-yl) derivatives, which are reactive intermediates. Substitution at the C4 position was then carried out by reactions with alkyl and aryl amines, and thiols. Typically, reactions were conducted as a two-step, one-pot transformation, and also as a one-step conversion. After examining the reactions, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang

Pharmacy Faculty Articles and Research

Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2',3'-dideoxy-5-fluoro-3'- thiacytidine (FTC), and 2',3'-dideoxy-3'-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides.

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Polypharmacy In Elderly: A Cautious Trail To Tread, Saniya Raghib Sabzwari, Waris Qidwai, Seema Bhanji

Department of Family Medicine

Polypharmacy has now increasingly come into focus as the recipient of healthcare in old age worldwide. In elderly it is associated with frequent adverse drug reactions (ADRs) and drug-drug interactions resulting in significant morbidity. Geriatrics is still an emerging specialty in South Asia, especially in Pakistan, where multiple reasons for polypharmacy exist. An extensive literature review of articles using key words like \'polypharmacy,\' \'elderly\' was conducted. The recently updated Beers Criteria of classification of inappropriate drugs in the elderly was reviewed in detail. Articles of relevance to polypharmacy and evaluation of guidelines for appropriate interventions to minimise inappropriate drug prescribing …

Developing Pentamethine Cyanine Dyes For Photodynamic Therapy, Quoc Bao H. Nguyen

Georgia State Undergraduate Research Conference

No abstract provided.

Asymmetric Total Synthesis Of Congeners Of Hydramycin, An Anthraquinone-Type Antitumor Agent, Costyl Ngnouomeuchi Njiojob

Doctoral Dissertations

Hydramycin is an antitumor antibiotic isolated from Streptomyces violaceus. It is a pyranoanthraquinone-type antitumor agent that has shown broad-spectrum activity against a variety of human-derived cancer cell lines. Among tumors evaluated at the National Cancer Institute (lung, colon, melanoma, breast and prostate), GI₅₀s were <10⁻¹⁰ M in the NCI's 60-cell-line panel. We embarked on the synthesis and evaluation of a simplified congener 2-(1-hydroxy-1-(oxiran-2-yl)ethyl)-4H-naphtho[2,3-h]chromene-4,7,12-trione(17), which would facilitate synthesis while retaining the potent activity. Hydramycin has two chiral centers, and our goal is to design and synthesize all the possible enantiomers (four in …

What Is New For An Old Molecule? Systematic Review And Recommendations On The Use Of Resveratrol, Ole Vang, Nihal Ahmad, Karen Brown, Anna Csiszar, Thomas Szekeres, Thomas Walle, Joseph M. Wu

NYMC Faculty Publications

BACKGROUND: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark.

METHODOLOGY: Literature search in databases as PUBMED and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of …

Synthesis Of Nucleoside 5′-O-Α,Β-Methylene-Β-Triphosphates And Evaluation Of Their Potency Towards Inhibition Of Hiv-1 Reverse Transcriptase, Yousef Ahmadibeni, Chandravanu Dash, M. J. Hanley, S. F. J. Le Grice, Hitesh K. Agarwal, Keykavous Parang

Pharmacy Faculty Articles and Research

A polymer-bound α,β-methylene-β-triphosphitylating reagent was synthesized and subjected to reactions with unprotected nucleosides, followed by oxidation, deprotection of cyanoethoxy groups, and acidic cleavage to afford nucleoside 5′-O-α,β-methylene-β-triphosphates. Among all the compounds, cytidine 5′-O-α,β-methylene-β-triphosphate inhibited RNase H activity of HIV-1 reverse transcriptase with a Ki value of 225 μM.

Antibiotics That Inhibit 30s Or 50s Ribosomal Subunit Formation: Hygromycin B, Quinupristin-Dalfopristin And Xrp 2868., Susan Mabe Mcgaha

Electronic Theses and Dissertations

Several antibiotics that prevent translation by binding to ribosomal subunits have been shown to also inhibit ribosomal subunit assembly (Champney and Tober 2003). The aminoglycoside hygromycin B was examined in Escherichia coli cells for inhibitory effects on translation and ribosomal subunit assembly. The streptogramin antibiotics quinupristin-dalfopristin and XRP 2868 (NXL 103) were examined for similar effects on these 2 cellular functions in antibiotic-resistant strains of Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae.

Pulse chase experiments were performed which verified slower rates of ribosomal subunit formation in drug treated cells. Hygromycin B exhibited a concentration dependent inhibitory effect …