Medicinal and Pharmaceutical Chemistry Commons^™

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 …

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 …