Medicinal and Pharmaceutical Chemistry Commons^™

Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli

Masters Theses & Specialist Projects

Platinum compounds are widely used drugs in cancer treatments. Although DNA is the biological target, reaction of platinum compounds with proteins is also potentially significant. Our objective is to study the effects of leaving ligands on the relative reactivity between 5'-GMP (guanosine 5' phosphate), a key DNA target, and N-Acetyl - L-Methionine (N-AcMet), a key protein target. We have used NMR spectroscopy to monitor reactions with N-AcMet and 5'-GMP added to a platinum complex to see which products are formed preferentially. Previous research showed that both a non-bulky complex such as [Pt(en)(D₂O)₂]²⁺ [en=ethylenediamine], and a …

A Series Of Pharmaceutical Technology Concepts Applied To Pediatric Formulations, Hao Lou

Theses and Dissertations (ETD)

Pediatric formulations have received great attention from regulatory agencies in the United States and Europe. Since solid dosage forms such as tablets and capsules will not be able to improve pediatric patients’ compliance, customized pediatric formulations are needed. In response, formulators in the pharmaceutical industry have made significant effort into developing various pediatric formulations. However, developing satisfactory pediatric formulations is a process that is guided by case by case basis. The objective of this current study was to apply the scientific pharmaceutical technology concepts into developing modern pediatric formulations. We have shown that the drug delivery design will be affected …

Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by …

Epigenetic Regulation Of Bmp2 By 1,25-Dihydroxyvitamin D3 Through Dna Methylation And Histone Modification., Baisheng Fu, Hongwei Wang, Jinhua Wang, Ivana Barouhas, Wanqing Liu, Adam Shuboy, David A. Bushinsky, Dongsheng Zhou, Murray J. Favus

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Genetic hypercalciuric stone-forming (GHS) rats have increased intestinal Ca absorption, decreased renal tubule Ca reabsorption and low bone mass, all of which are mediated at least in part by elevated tissue levels of the vitamin D receptor (VDR). Both 1,25-dihydroxyvitamin D3(1,25(OH)2D3) and bone morphogenetic protein 2 (BMP2) are critical for normal maintenance of bone metabolism and bone formation, respectively. The complex nature of bone cell regulation suggests a potential interaction of these two important regulators in GHS rats. In the present study, BMP2 expression is suppressed by the VDR-1,25(OH)2D3 complex in Bone Marrow Stromal Cells (BMSCs) from GHS and SD …

Simvastatin: A Risk Factor For Angioedema?, Sarah A. Nisly, Areeba Kara, Tamara B. Knight

Scholarship and Professional Work – COPHS

Objective. To report a case of simvastatin-induced angioedema in a patient with near nightly episodes of orofacial angioedema.

Case Summary. A 75-year-old African American female presented to the emergency department with recurrent face, lip, and tongue swelling. The patient described frequent episodes of orofacial edema, with 4 emergency department visits over the previous 6 months. Her home medications were reviewed and simvastatin was identified as a possible contributing medication. Simvastatin was discontinued with resolution of the symptoms during hospitalization and a significant reduction in episodes.

Discussion. Drug-induced angioedema has been documented with several agents, most commonly angiotensin-converting enzyme inhibitors. …

Canagliflozin, A New Sodium-Glucose Co-Transporter 2 Inhibitor, In The Treatment Of Diabetes, Sarah A. Nisly, Denise M. Kolanczyk, Alison M. Walton

Scholarship and Professional Work – COPHS

Purpose. The published evidence on the pharmacology, pharmacodynamics, pharmacokinetics, safety, and efficacy of a promising investigational agent for managing type 2 diabetes is evaluated.

Summary. Canagliflozin belongs to a class of agents—the sodium–glucose cotransporter 2 (SGLT2) inhibitors—whose novel mechanism of action offers potential advantages over other antihyperglycemic agents, including a relatively low hypoglycemia risk and weight loss-promoting effects. Canagliflozin has dose-dependent pharmacokinetics, and research in laboratory animals demonstrated high oral bioavailability (85%) and rapid effects in lowering glycosylated hemoglobin (HbA1c) values. In four early-stage clinical trials involving a total of over 500 patients, the use of canagliflozin for varying periods …

Vancomycin And Gentamicin Pharmacokinetic Alterations In An Adolescent Amputee, Kristen R. Nichols, Kari M. Edison, Michelle D. Rosenbaum, Chad A. Knoderer

Scholarship and Professional Work – COPHS

A 14-year-old male with bilateral above-the-knee amputations presented to our hospital for treatment of a skin and soft-tissue infection. We report the experience of vancomycin and gentamicin therapy in this patient. Because these medications require weight-based dosages and pharmacokinetic monitoring of serum levels, it was necessary to obtain peak and trough levels of the two drugs in order to determine the pharmacokinetic differences in this patient compared to those in an adolescent male without amputations. To our knowledge, this is the first report describing pharmacokinetic differences in an adolescent amputee.

Medical Marijuana Legislation: What We Know - And Don't, Linda Simoni-Wastila, Francis B. Palumbo

Journal of Health Care Law and Policy

No abstract provided.

The Best Of Both Worlds: Applying Federal Commerce And State Police Powers To Reduce Prescription Drug Abuse, Michael C. Barnes, Gretchen Arndt

Journal of Health Care Law and Policy

No abstract provided.

Investigating Key Post-Pks Enzymes From Gilvocarcin Biosynthetic Pathway, Nidhi Tibrewal

Theses and Dissertations--Pharmacy

Gilvocarcin V (GV) belongs to the angucycline class of antibiotics that possesses remarkable anticancer and antibacterial activities with low toxicity. Gilvocarcin exhibits its light induced anticancer activity by mediating crosslinking between DNA and histone H3. When photo-activated by near-UV light, the C8 vinyl group forms a [2+2] cycloadduct with thymine residues of double stranded DNA. _D-fucofuranose is considered essential for histone H3 interactions. However, the poor water solubility has rendered it difficult to develop gilvocarcin as a drug. We aim to design novel gilvocarcin analogues with improved pharmaceutical properties through chemo-enzymatic synthesis and mutasynthesis. Previous studies have characterized many …

Testosterone Use And Effects, Brandon Mills

Natural Sciences Student Research Presentations

Summarizes the chemical make-up, medical applications and side effects for the steroidal hormone Testosterone. This is a project for the Natural Sciences Poster Session at Parkland College.

The Antiinflammatory Action And Pharmacokinetics Of A Novel Glucosamine-Based Di-Peptide Aminosugar, Mohammad H. Gilzad-Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

Purpose. We have previously shown favorable in vitro gut permeability for three novel dipeptide esters of glucosamine (GlcN) likely facilitated by the peptide transporter 1 (PepT1). Herein, we report the development of a novel assay for the determination of bioavailability of the peptide ester of interest, the anti-inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as well as its pharmacokinetics under healthy and inflammatory conditions.

Methods. A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that were cannulated in their right jugular vein for …

Menthol Binding And Inhibition Of A7-Nicotinic Acetylcholine Receptors, Abrar Ashoor, Jacob C. Nordman, Daniel Veltri, Keun-Hang Susan Yang, Lina T. Al Kury, Yaroslav M. Shuba, Mohamed Magoub, Frank Christopher Howarth, Bassem Sadek, Amarda Shehu, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol is a common compound in pharmaceutical and commercial products and a popular additive to cigarettes. The molecular targets of menthol remain poorly defined. In this study we show an effect of menthol on the α7 subunit of the nicotinic acetylcholine (nACh) receptor function. Using a two-electrode voltage-clamp technique, menthol was found to reversibly inhibit α7-nACh receptors heterologously expressed in Xenopus oocytes. Inhibition by menthol was not dependent on the membrane potential and did not involve endogenous Ca2+-dependent Cl− channels, since menthol inhibition remained unchanged by intracellular injection of the Ca2+ chelator BAPTA and perfusion with Ca2+-free bathing solution containing …

Binding Of An Indenoisoquinoline To The Topoisomerase-Dna Complex Induces Reduction Of Linker Mobility And Strengthening Of Protein-Dna Interaction., Giordano Mancini, Ilda D'Annessa, Andrea Coletta, Giovanni Chillemi, Yves Pommier, Mark S. Cushman, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Long-duration comparative molecular dynamics simulations of the DNA-topoisomerase binary and DNA-topoisomerase-indenoisoquinoline ternary complexes have been carried out. The analyses demonstrated the role of the drug in conformationally stabilizing the protein-DNA interaction. In detail, the protein lips, clamping the DNA substrate, interact more tightly in the ternary complex than in the binary one. The drug also reduces the conformational space sampled by the protein linker domain through an increased interaction with the helix bundle proximal to the active site. A similar alteration of linker domain dynamics has been observed in a precedent work for topotecan but the molecular mechanisms were different …

High Resolution Mass Spectrometry (Hrms) Based Investigation Of Small Molecule, Bioactive Secondary Metabolites As Probes In The Examination Of Bacterial Resistance And Virulence, Jerrod Stephen Scarborough

Theses and Dissertations (ETD)

The widespread availability of antimicrobial chemotherapeutics over the last half of the twentieth century has offered dramatic increases in life expectancy. Unfortunately, many pathogenic agents are exhibiting ever increasing resistance to many frontline antibiotics. New chemotherapeutic agents are urgently needed to combat this threat; this work seeks to illustrate applications in which mass spectrometric techniques may be applied to the investigation of novel, small molecule chemotherapeutics for the treatment of bacterial infections. Chapter 1 contains an introduction to mass spectrometry, as well as an overview of relevant chromatographic techniques. Chapter 2 introduces the bacterium F tularensis and M ulcerans and …

Plk1 Phosphorylation Of Orc2 And Hbo1 Contributes To Gemcitabine Resistance In Pancreatic Cancer, Bing Song, X Shawn Liu, Steven J. Rice, Shihuan Kuang, Bennett D. Elzey, Stephen F. Konieczny, Timoty L. Ratliff, Tony R. Hazbun, Elena G. Chiorean, Xiaoqi Liu

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Although gemcitabine is the standard chemotherapeutic drug for treatment of pancreatic cancer, almost all patients eventually develop resistance to this agent. Previous studies identified Polo-like kinase 1 (Plk1) as the mediator of gemcitabine resistance, but the molecular mechanism remains unknown. In this study, we show that Plk1 phosphorylation of Orc2 and Hbo1 mediates the resistance to gemcitabine. We show that the level of Plk1 expression positively correlates with gemcitabine resistance, both in pancreatic cancer cells and xenograft tumors. Overexpression of Plk1 increases gemcitabine resistance, while inhibition of Plk1 sensitizes pancreatic cancer cells to gemcitabine treatment. To validate our findings, we …

Development Of The Sustained Release Analgesic Formulations For Rodents And A Novel In Vitro Model For Parenteral Formulations With The Character Of A Level A Ivivc, Jin Xu

Theses and Dissertations (ETD)

Laboratory animals are often subjected to various painful surgical procedures such as laparotomy, thoracotomy or orthopedic procedures as well as non-surgical procedures such as the induction of arthritis. Any procedure that causes pain in humans is assumed to cause pain in animals too. It is the ethical obligation of all research personnel to reduce or preferably eliminate pain and distress by using analgesics. Furthermore, the Institutional Animal Care and Use Committee (IACUC) requires that appropriate anesthetics and/or analgesics must be used to minimize or eliminate pain and distress for animals undergoing painful procedures.

The oral administration route is the most …

Development Of A Men’S Preference For Testosterone Replacement Therapy (P-Trt) Instrument, Sheryl L. Szeinbach, Enrique Seoane-Vazquez, Kent H. Summers

Pharmacy Faculty Articles and Research

Background: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument.

Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men’s P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and …

Portable Bacterial Identification System Based On Elastic Light Scatter Patterns, Euiwon Bae, Dawei Ying, Donald Kramer, Valery Patsekin, Bartek Rajwa, Cheryl Holdman, Jennifer Sturgis, Vincent J. Davisson, J Paul Robinson

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Conventional diagnosis and identification of bacteria requires shipment of samples to a laboratory for genetic and biochemical analysis. This process can take days and imposes significant delay to action in situations where timely intervention can save lives and reduce associated costs. To enable faster response to an outbreak, a low-cost, small-footprint, portable microbial-identification instrument using forward scatterometry has been developed.

Results

This device, weighing 9 lb and measuring 12 × 6 × 10.5 in., utilizes elastic light scatter (ELS) patterns to accurately capture bacterial colony characteristics and delivers the classification results via wireless access. The overall system consists of …

Design, Synthesis And Biological Evaluation Of Novel Cannabinoid Antagonist, Abha Verma

LSU New Orleans Theses and Dissertations

This study was aimed at the development of novel CB1 cannabinoid receptor antago­nists that may have clinical applications for the treatment of cannabinoid and psychostimulant addiction. The rationale for the design for our target was to incorporate a bioisosteric 1,2,3-triazole ring into the vicinal diaryl group revealed in the prototypical antagonist/inverse agonist SR141716 (Rimonabant) that was pre­sumed to interact with a unique region in the CB1 receptors. Based on our prelimi­nary results we identified a novel series of 1,2,3-triazole ester and keto deriva­tives as lead compounds for biological evaluation. Here in the design rationale, syn­thesis and CB1 receptor affinity for …