Medicinal and Pharmaceutical Chemistry Commons^™

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

An Analysis Of The Cause, Effect & Control Of Hyperlipidemia From A Nursing Perspective, Melissa Rodgers

Theses and Dissertations

Two of the top four causes of death worldwide, heart disease and stroke, are related to hyperlipidemia, elevated cholesterol levels; these two illnesses account for approximately seventeen million deaths each year (World Health Organization, 2014). In order to combat the prevalence of these illnesses, the National Cholesterol Educational Panel has issued guidelines regarding cholesterol management. Extensive research has been published concerning cholesterol management. However, a gap remains between evidenced-based practice and community awareness of this phenomenon. This manuscript compiles research from peer reviewed nursing journals and acclaimed government and national organizations to express the cause, effect, and control of hyperlipidemia …

Dorothy Crowfoot Hodgkin: Captured For Life By Chemistry And Crystals, Andrea L. Rice

Natural Sciences Student Research Presentations

Dorothy Crowfoot Hodgkin's pioneering work in X-ray chrystallography made a lasting impact on many scientific fields, including medicine and biochemistry. Her discoveries paved the way for others to devleop new antibiotics, cancer treatments and imaging techniques.

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Beta-Blockers Act Through Clathrin-Dependent Internalization And Egfr Transactivation To Promote Erk Phosphorylation, Taiwo Ajumobi

Graduate Thesis Collection

For cardiovascular diseases such as high blood pressure, angina pectoris, and left ventricle hypertrophy; long-term activation of beta-adrenergic receptors is strongly linked to the progression of these diseases. A class of antagonistic drugs that target betaadrenergic receptors are collectively called beta-blockers. These drugs are commonly used to reduce the inotropic and chronotropic effects of beta-adrenergic receptor activation. This past decade has revealed that beta-blockers and other ligands are capable of functional selectivity at receptors. Functional selectivity describes the ability of ligands acting at 0 protein-coupled receptors (OPCRs) to preferentially activate or inhibit different signal transduction pathways. The studies on beta-adrenergic …

Development Of Bivalent Ligands Targeting The Putative Ccr5-Mor Heterodimer, Thomas Raborg

Theses and Dissertations

Chemokine receptor CCR5 (CCR5) is a G-protein coupled receptor (GPCR) predominantly expressed on leukocytes, or white blood cells.1–3 During inflammation, the body releases chemokines that bind to receptors such as CCR5 and attract leukocytes to the area of inflammation, leading to an immunological response.1 CCR5 is also an important receptor in the human immunodeficiency virus's (HIV-1) invasion of host cells, as CCR5 acts as a co-receptor that facilitates HIV-1 viral entry.4,5 The continued destruction of leukocytes as a result of HIV-1 viral entry produces a disease state called acquired immunodeficiency syndrome (AIDS).5 Of note, this receptor is also expressed on …

Hydropathic Interactions And Protein Structure: Utilizing The Hint Force Field In Structure Prediction And Protein‐Protein Docking., Mostafa H. Ahmed

Theses and Dissertations

Protein structure predication is a field of computational molecular modeling with an enormous potential for improvement. Side-chain geometry prediction is a critical component of this process that is crucial for computational protein structure predication as well as crystallographers in refining experimentally determined protein crystal structures. The cornerstone of side-chain geometry prediction are side-chain rotamer libraries, usually obtained through exhaustive statistical analysis of existing protein structures. Little is known, however, about the driving forces leading to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines extracted from the PDB reveals their …

Meta-Analysis Of Herbal Cannabis Therapy For Chronic Pain, Michael J. Seneca

UNF Graduate Theses and Dissertations

Since the first so-called “medical marijuana” legislation was passed in California in 1996, a total of twenty states and the District of Columbia have passed laws permitting limited use of cannabis. Despite the changes in state laws, cannabis remains illegal for any purpose under federal law. Changes in state laws have coincided with a renewed interest in the substance for the treatment of a variety of conditions. There has been a significant increase in published data over the past twenty years examining the efficacy of cannabis as an appetite stimulant, antiemetic agent, and analgesic adjuvant. The purpose of this meta-analysis …

Structure Based Identification And Characterization Of Flavonoids That Disrupt Human Papillomavirus-16 E6 Function, Elliot J. Androphy, Jonathan J. Cherry, Anne Rietz, Anna Malinkevich, Yuqi Liu, Meng Xie, Matthew D. Bartolowits, Vincent J. Davisson, James D. Baleja

Department of Medicinal Chemistry and Molecular Pharmacology Graduate Student Publications

Expression and function of the human papillomavirus (HPV) early protein 6 (E6) is necessary for viral replication and oncogenesis in cervical cancers. HPV E6 targets the tumor suppressor protein p53 for degradation. To achieve this, “high-risk” HPV E6 proteins bind to and modify the target specificity of the ubiquitin ligase E6AP (E6 associated protein). This E6-dependent loss of p53 enables the virus to bypass host cell defenses and facilitates virally induced activation of the cell cycle progression during viral replication. Disruption of the interaction between E6 and E6AP and stabilization of p53 should decrease viability and proliferation of HPV positive …

Synthesis Of Novel Azetidines, Amber Thaxton

LSU New Orleans Theses and Dissertations

Azetidine is a four-membered nitrogen-containing heterocyclic ring that has recently received a great deal of attention as a molecular scaffold for the design and preparation of biologically active compounds. Structure-activity studies employing functionalized azetidines have led to the development of variety of drug molecules and clinical candidates encompassing a broad spectrum of biological activities.

Herein, the synthesis a novel series of 3-aryl-3-arylmethoxyazetidines is described. Selected 3-aryl-3-arylmethoxyazetidines were evaluated for their binding affinity to multiple monoaminergic transporters for the potential treatment of methamphetamine addiction. It was discovered that this scaffold exhibits high binding affinity (nM) for both the serotonin and dopamine …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Investigating Intermolecular Interactions In Crystalline Aspirin Using Cdft, Nicholas Turner, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Drugs today are widely administered in their crystalline form, namely via tablets and capsules. The crystal structure of a drug molecule affects important drug qualities such as solubility, bioavailability, shelf life, and compaction properties. In order to form a basis for crystal structure prediction, it is necessary to first understand how intermolecular interactions cause molecules to pack in certain ways. Being able to predict and perhaps even control a drug molecule’s crystal structure will lead to the development of higher quality drugs that perform more consistently. Scientists and engineers do not fully understand the reasons for a molecule assuming a …

Solvent Dependency Of The Uv-Vis Spectrum Of Indenoisoquinolines: Role Of Keto-Oxygens As Polarity Interaction Probes., Andrea Coletta, Silvia Castelli, Giovanni Chillemi, Nico Sanna, Mark S. Cushman, Yves Pommier, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB inhibitors. We present an integrated experimental/computational investigation of the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical trials. In all the three compounds a similar dependence of the relative absorption intensities at 270 nm and 290 nm on solvent polarity is found. The keto-oxygens in positions 5 and 11 of the molecular scaffold of the molecule are the principal chromophores involved in this dependence. Protic interactions on these sites are also found to give rise to absorptions at wavelengthsolution, …

A Standardized Patient Counseling Rubric For A Pharmaceutical Care And Communications Course, Niambi Horton Pharmd, Kenna D. Payne Pharmd, Michelle Jernigan Pharmd, Jill Frost Pharmd, Stephen Wise Pharmd, Mary Klein Pharmd, Joel Epps Mba, H. Glenn Anderson Pharmd

Pharmaceutical Science and Research

Objective. To restructure a required pharmaceutical care and communications course to place greater emphasis on communication skills and include a high-stakes assessment.

Design. A standardized counseling rubric was developed for use throughout the pharmacy curriculum and the counseling laboratory practicals were changed to high-stakes assessments.

Assessment. An annual mid-semester and end-of-semester high-stakes patient-counseling objective structured clinical examination (OSCE) conducted prior to and after revision of the course and counseling rubric documented improvements in students’ scores. Performance on the post-course annual assessment patient counseling OSCE improved compared to that on the pre-course (p,0.001).

Conclusion. The 2010 course revision improved …

Controlling The Size And Shape Of Polypeptide Colloidal Particles: Temperature Dependence Of Particle Formation, John P. Gavin, Nolan B. Holland, Kiril A. Streletzky

Undergraduate Research Posters 2013

A promising approach for developing new drug delivery vehicles is by using stimuli responsive hydrogel nanoparticles. Polypeptide surfactants designed in our lab have been shown to form micellar particles of varying sizes and shapes depending on the solution salt concentration. These responsive polypeptide surfactants consist of a small charged protein domain (foldon) with three elastin-like polypeptide (ELP) chains forming a three-armed star polymer. The size and shape of the micelles they form is dependent on the ratio of total ELP volume to head group area. By introducing linear ELP into the ELP-foldon solution, the total volume of ELP in the …

Single Step Synthesis Of Antibiotic Kanamycin Embedded Gold Nanoparticles For Efficient Antibacterial Activity, Shravan Gavva

Masters Theses & Specialist Projects

Nanotechnology has become the most advanced type of drug delivery system within the last decade. This advancement shifted the focus on small carriers to increase the efficiency of the drugs. Among these, gold nanoparticles (GNPs) were found to have profound biomedical applications. In current research, kanamycin embedded GNPs were prepared in a single step, single phase, and bio-friendly (green synthesis) procedure. The synthesized Kanamycin-GNPs (Kan-GNPs) were spherical in shape and had a size range of 15 ± 3 nm. The chosen kanamycin is an aminoglycosidic antibiotic that is isolated from Streptomyces kanamyceticus. These special antibiotic GNPs are further characterized using …

Development Of Tools To Assess The Effects Of Lunasin On Normal Development And Tumor Progression In Drosophila Melanogaster, Gillian E. Jones

Masters Theses & Specialist Projects

Soy contains many bioactive molecules known to elicit anti-cancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells while having no cytotoxic effect on non-tumorigenic or established cancer cell lines. In this study we attempt to understand the developmental effects of Lunasin overexpression in vivo and create reagents that will help us understand Lunasin’s anti tumorigenic effects in an intact organism. cDNA encoding lunasin and EGFP-lunasin were cloned into pUAST and microinjected into Drosophila embryos. Tissue-specific overexpression of EGFP-Lun in the resulting transgenic lines was accomplished by crossing transgenics to various GAL4 driver lines. …

Design, Development, And Characterization Of Novel Antimicrobial Peptides For Pharmaceutical Applications, Yazan H. Akkam

Graduate Theses and Dissertations

Candida species are the fourth leading cause of nosocomial infection. The increased incidence of drug-resistant Candida species has emphasized the need for new antifungal drugs. Histatin 5 is a naturally occurring human salivary antifungal peptide and the first line of defense against infections of the oral cavity. This research has focused on understanding the activity of histatin 5, and subsequently designing novel peptides that may serve as models for the further development of therapeutics to treat fungal infection.

This objective has been achieved in three steps: studying the structural requirement of histatin 5 involved in antifungal activity, the identification of …

Isolation And Partial Characterization Of Bioactive Fucoxanthin From Himanthalia Elongata Brown Seaweed: A Tlc-Based Approach, Gaurav Rajauria, Nissreen Abu-Ghannam

Articles

Seaweeds are important sources of carotenoids, and numerous studies have shown the beneficial effects of these pigments on human health. In the present study, Himanthalia elongata brown seaweed was extracted with a mixture of low polarity solvents, and the crude extract was separated using analytical thin-layer chromatography (TLC).The separated compounds were tested for their potential antioxidant capacity and antimicrobial activity against Listeria monocytogenes bacteria using TLC bioautography approach. For bio-autography, the coloured band on TLC chromatogram was visualized after spraying with DPPH and triphenyltetrazolium chloride reagents which screen antioxidant and antimicrobial compounds, respectively, and only one active compound was screened …

Synthesis And Biological Evaluation Of Novel Folic Acid Receptor-Targeted, Β-Cyclodextrin-Based Drug Complexes For Cancer Treatment., Juan-Juan Yin, Sonali Sharma, Stepan P. Shumyak, Zhi-Xin Wang, Zhi-Wei Zhou, Yangde Zhang, Peixuan Guo, Chen-Zhong Li, Jagat R. Kanwar, Tianxin Yang, Shyam S. Mohapatra, Wanqing Liu, Wei Duan, Jian-Cheng Wang, Qi Li, Xueji Zhang, Jun Tan, Lee Jia, Jun Liang, Ming Q. Wei, Xiaotian Li, Shu-Feng Zhou

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily …