Medicinal and Pharmaceutical Chemistry Commons^™

Design, Synthesis, And Evaluation Of Aryl Hydantoins And Ureas As Antischistosomal Agents, Chunkai Wang

Theses & Dissertations

Schistosomiasis is a tropical parasitic disease caused by infections with flukes of the genus Schistosoma, affecting as many as 440 million individuals worldwide, with 779 million living at risk of infection. A new drug for schistosomiasis is urgently needed as praziquantel (PZQ) is currently the drug of last resort and the development of resistance cannot be ignored, particularly in view of its large-scale use in many endemic countries. Furthermore, PZQ is active against adult but not juvenile schistosomes; this may be an important factor in the frequently observed treatment ‘failures’ in areas endemic for schistosomiasis.

The introduction of PZQ in …

Pharmacotherapeutic Considerations For Individuals With Down Syndrome, Erik Hefti

Harrisburg University Faculty Works

Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight …

Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo

Doctoral Projects

Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Synthesis Of Huacat® Analogues As Novel Organocatalysts For The Formation Of Asymmetric C-C Bonds, Kenneth Laboy

Loma Linda University Electronic Theses, Dissertations & Projects

The synthesis of organic compounds with preferential stereochemistry is ubiquitous in the scientific community. A chemical reaction that asymmetrically induces one stereoisomer over another is achieved through the use of catalysts and various coupling reagents.1 Inorganic catalysts, such as TiCl4 and ZnCl2, have been documented for many decades as effective agents in the synthesis of asymmetric bonds, however, there are environmental limitations to their use. First, the asymmetric reactions involving these metal catalysts require solvents that are not environmentally-friendly, especially when used on an industrial scale and second, the metal catalysts are recycled when possible, however, there is always metal …

Rnai Nanotechnology: A Platform For Sirna Screening And Cancer Gene Therapy, Mayurbhai Ravikant Patel

Seton Hall University Dissertations and Theses (ETDs)

Over the past two decades, advances in RNA structural biology have improved our understanding of the structures and folding properties of naturally occurring RNAs. RNA sequences and structures participate in many specific biological functions, such as those performed by messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), micro RNA (miRNA), short-interfering RNA (siRNA), small nuclear RNA (snRNA) and many others. The noncoding RNAs, such as siRNA, do not express proteins but have been utilized in a wide range of applications, including RNA interference (RNAi) and the regulation of mRNA expression. These important biological functions have been implemented in gene …

Repeated Zolpidem Treatment Effects On Sedative Tolerance, Withdrawal, Mrna Levels, And Protein Expression, Brittany T. Wright

Theses and Dissertations (ETD)

Zolpidem and benzodiazepines (BZs) potentiate the inhibitory action of gamma-Aminobutyric acid (GABA) by allosterically binding to GABAA receptors (GABAAR). Prolonged use of GABAAR positive allosteric modulators (PAM) can lead to behavioral tolerance, the diminished response to the same drug dose with repeated use, and withdrawal, a group of symptoms that occur due to abrupt end of drug treatment. Zolpidem is a short-acting, non-BZ GABAAR PAM whose potential for tolerance and withdrawal is unclear. Zolpidem demonstrates sedative efficacy similar to BZs and has become a main treatment of insomnia in lieu of BZs. Zolpidem replaced BZs due to lower incidences of …

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts …

Incidence Of Hypomagnesemia On Proton Pump Inhibitors At The Huntington Veterans Affairs Medical Center – Ihop, Ebrahim Sabbagh, Do, Chelsey R. Houchins, James Allman, Ii, Pharmd, Samson Teka, Md

Marshall Journal of Medicine

Abstract

Title: Incidence of hypomagnesemia on proton pump inhibitors at the Huntington Veterans Affairs Medical Center – IHOP

Purpose:

Proton pump inhibitors (PPIs), both prescription and over-the-counter, are widely used for the treatment of acid-related disease states such as dyspepsia, gastroesophageal reflex disease, esophagitis, and peptic ulcers. These medications are generally considered safe in most patient populations; however, there are several adverse effects that may occur with long-term use. Hypomagnesemia is a newer complication arising in the literature following multiple case reports over the past several years, although the true incidence of hypomagnesemia associated with PPI use remains unclear at …

Upregulation Of Antibiotic Activity Of A Streptomyces Sp. Via Co-Cultures With Challenge Pathogens, Anne A. Sung

Honors Scholar Theses

Marine natural product drug discovery has begun to play an important role in the treatment of diseases. Early drug discovery from natural products came primarily from plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms. Numerous natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity in the production of biologically active secondary metabolites. Ascidians, also known as tunicates, are marine invertebrates that contain many host-associated microbes. Adult tunicates are sessile, which makes them vulnerable to predators, and thus, they …

Hit Identification For Pkcζ Inhibitors: Structure-Based Optimization, Virtual Screening, And Biological Evaluation, Xiaoxin Wu

Theses and Dissertations (ETD)

Protein kinase C ζ (PKCζ) is believed to be a promising target for the treatment of some diseases, including inflammatory diseases, obesity and diabetes. Hit identification of PKCζ inhibitors was conducted by structure-based modification, virtual screening and biological evaluation. Among all the compounds selected and synthesized, compound JW-1-60A showed moderate activity against PKCζ at 30 μM and 100 μM. The molecular modeling studies showed that the binding mode of JW-1-61A was very close to the binding mode of JP-3-149, a reported PKCζ inhibitor with very potent activity, which might partially explain the moderate activity of JW-1-61A. Based on the structure …

2016 Touro College Of Pharmacy Senior Yearbook, College Of Pharmacy

Touro Yearbooks

2016 College of Pharmacy Senior Yearbook

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

A Descriptive Investigation Of The Impact Of Student Research Projects Arising From Elective Research Courses, Sam Harirforoosh, David W. Stewart

Pharmacy Faculty Articles and Research

Background: Pharmacy academicians have noted the need to develop research skills in student pharmacists. At the Gatton College of Pharmacy, significant focus has been placed on the development of research skills through offering elective research courses. In order to evaluate the impact of participation in the research elective(s), we analyzed college records and surveyed faculty members with regard to the number of poster/podium presentations, published peer-reviewed manuscripts, and funded projects.

Results: Student enrollment in the research elective sequence has increased over time and has resulted in 81 poster presentations, 14 podium presentations, and 15 peer-reviewed publications.

Conclusions: …

Nucleosome Distortion As A Possible Mechanism Of Transcription Activation Domain Function, Tamara Y. Erkina, Alexandre M. Erkine

Scholarship and Professional Work – COPHS

After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct recruitment by ADs of co-activators and basal transcriptional machinery components, however, is not always compatible with the short size yet very high degree of sequence randomness and intrinsic structural disorder of natural and synthetic ADs. In this review, we formulate the basis for an alternative and complementary model, whereby sequence randomness and intrinsic structural disorder of ADs are necessary for transient distorting interactions with promoter nucleosomes, triggering promoter nucleosome translocation and …

Whole Genome Sequence Analysis Of The Tallyho/Jng Mouse, James Denvir, Goran Boskovic, Jun Fan, Donald A. Primerano, Jacaline K. Parkman, Jung Han Kim

Biochemistry and Microbiology

Background: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes.

Results: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64.8X coverage using data from three next generation sequencing …

Improving The Renal Profile Of A Hiv Drug Combination Through Prodrug Alteration, Derek E. Murrell, Sam Harirforoosh

Pharmacy Faculty Articles and Research

"Human immunodeficiency virus (HIV) continues to alter the lives of countless individuals, who once infected, live on a continuum between viral suppression and acquired immunodeficiency syndrome. The former being achieved via the use of various antiretrovirals beginning with the release of zidovudine over a quarter-century ago; whereas the latter may result from treatment failure or lack of treatment such as in the absence of diagnosis or the inaccessibility of medication. As no cure is yet available, regimens must be continued lifelong. Thus, contemporary treatment is given as a combination of agents from various antiretroviral drug classes in an effort to …

Synthesis, Characterization, And In Vitro Anti-Tumor Studies Of Bis Imidazolium Salts With Alkyl Chain Linkers And Naphthylmethyl Substituents, Steven R. Crabtree

Williams Honors College, Honors Research Projects

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N¹ and N^1’ positions for a structure-activity relationship (SAR) study. All compounds were characterized by ¹H and ¹³C NMR spectroscopy. The cationic portion of 2 as the PF₆ salt, 3, 4, and 5 were also characterized by single-crystal X-ray crystallography. Compounds 1-8, 10, and 12 were tested for their in vitro anti-cancer activity against four NSCLC cell lines via the MTT assay (NCI–H460, NCI–H1975, HCC827, and A549). Compounds 10 and 12 which …

The Effects Of Amixicile, A Pyruvate Ferredoxin Oxidoreductase Inhibitor, On Oral Treponemes, Lucas A. Reed

Theses and Dissertations

Periodontal disease (PD) is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption, and tooth loss (edentulism). Treponema denticola along with Porphyromonas gingivalis and Tannerella forsythia are among the “Red Complex” and are main etiological agents in PD. Treponemes are a member of the Spirochaeta phylum and are obligate anaerobes, that express pyruvate ferredoxin oxidoreductase (PFOR). The enzyme catalyzes the oxidation of pyruvate to acetyl-CoA and reduced ferredoxin. Amixicile is a novel bacteriostatic derivative of nitazoxanide and an inhibitor of PFOR. In light of the fact that Treponemes express PFOR, this study was conducted to investigate the …

Examination Of The Pharmacodynamics And Pharmacokinetics Of A Diclofenac Poly(Lactic-Co-Glycolic) Acid Nanoparticle Formulation In The Rat, Sam Harirforoosh, Kelsi O. West, Derek E. Murrell, James W. Denham, Peter C. Panus, Greg A. Hanley

Pharmacy Faculty Articles and Research

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assembled into two categories; cyclooxygenase (COX-1) sparing inhibitors of COX-2 and non-selective NSAIDs. Diclofenac (DICLO) is a non-selective NSAID that has been linked to serious side effects including gastric ulcers and renal injury. In this study, we examine the effect of poly(lactic-co-glycolic) acid nanoformulation on DICLO-associated adverse events and pharmacokinetics using a nanoparticle (NP) formulation previously developed in our laboratory.

MATERIALS AND METHODS: Rats were administered a single dose of methylcellulose (VEH), blank NP, DICLO (10 mg/kg), or a DICLO-NP suspension equivalent to the DICLO dose. Urinary and blood parameters were measured …