Medicinal and Pharmaceutical Chemistry Commons^™

Exacerbation Of Celecoxib-Induced Renal Injury By Concomitant Administration Of Misoprostol In Rats, Dustin L. Cooper, Derek E. Murrell, Christopher M. Conder, Victoria E. Palau, Grace E. Campbell, Shaun P. Lynch, James W. Denham, Angela V. Hanley, Kenny W. Bullins, Peter C. Panus, Krishna Singh, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters …

Design And Optimization Of Plga-Based Diclofenac Loaded Nanoparticles, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or …

Adverse Effects Of Nonsteroidal Anti-Inflammatory Drugs: An Update Of Gastrointestinal, Cardiovascular, And Renal Complications, Sam Harirforoosh, Waheed Asghar, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor’s …

A Genome-Wide Association Study Identifies A Locus On Tert For Mean Telomere Length In Han Chinese., Yun Liu, Lan Cao, Zhiqiang Li, Daizhan Zhou, Wanqing Liu, Qin Shen, Yanting Wu, Dan Zhang, Xun Hu, Ting Wang, Junyi Ye, Xiaoling Weng, Hong Zhang, Di Zhang, Zhou Zhang, Fatao Liu, Lin He, Yongyong Shi

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Leukocyte telomere length (LTL) is a predictor of aging and a number of age-related diseases. We performed genome-wide association studies of mean LTL in 2632 individuals,with a two-stage replication in 3917 individuals from Chinese populations. To further validate our findings, we get the results of 696 samples from a cohort of European ancestry. We identified two loci associated with LTL that map in telomerase reverse transcriptase (TERT; rs2736100, P = 1.93×10−5) on chromosome 5p15.33 and near keratin 80 (KRT80; rs17653722, P = 6.96×10−6) on 12q13.13. In Chinese population each C allele of rs2736100 and T allele …

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 …

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 …

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 …

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 …

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 …

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 …