Chemicals and Drugs Commons^™

Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo

Forensic Science Theses

Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …

Titanocene−Gold Complexes Containing N‑Heterocyclic Carbene Ligands Inhibit Growth Of Prostate, Renal, And Colon Cancers In Vitro, Yiu Fung Mui, Jacob FernáNdez-Gallardo, Benelita T. Elie, Ahmed Gubran, Irene Maluenda, Mercedes Sanau, Marıá Contel

Publications and Research

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5-C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer …

“Zipped Synthesis” By Cross-Metathesis Provides A Cystathionine Β‑Synthase Inhibitor That Attenuates Cellular H2S Levels And Reduces Neuronal Infarction In A Rat Ischemic Stroke Model, Christopher D. Mccune, Su Jing Chan, Matthew L. Beio, Weijun Shen, Woo Jin Chung, Laura M. Szczesniak, Chou Chai, Shu Qing Koh, Peter T.-H. Wong, David B. Berkowitz

David Berkowitz Publications

The gaseous neuromodulator H₂S is associated with neuronal cell death pursuant to cerebral ischemia. As cystathionine β-synthase (CBS) is the primary mediator of H2S biogenesis in the brain, it has emerged as a potential target for the treatment of stroke. Herein, a “zipped” approach by alkene cross-metathesis into CBS inhibitor candidate synthesis is demonstrated. The inhibitors are modeled after the pseudo-C₂-symmetric CBS product (L,L)-cystathionine. The “zipped” concept means only half of the inhibitor needs be constructed; the two halves are then fused by olefin cross-metathesis. Inhibitor design is also mechanism-based, exploiting the favorable kinetics associated with …

Theoretical Investigation Of Interaction Between The Set Of Ligands And Α7 Nicotinic Acetylcholine Receptor, O. E. Glukhova, Tatiana Prytkova, D. S. Shmygin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nicotinic acetylcholine receptors (nAChRs) are neuron receptor proteins that provide a transmission of nerve impulse through the synapses. They are composed of a pentametric assembly of five homologous subunits (5 α7 subunits for α7nAChR, for example), oriented around the central pore. These receptors might be found in the chemical synapses of central and peripheral nervous system, and also in the neuromuscular synapses. Transmembrane domain of the one of such receptors constitutes ion channel. The conductive properties of ion channel strongly depend on the receptor conformation changes in the response of binding with some molecule, f.e. acetylcholine. Investigation of interaction between …

Anticancer, Biophysical And Computational Investigations Of Half-Sandwich Ruthenium(Ii) Thiosemicarbazone Complexes: The Effect Of Arene Versus Thiacrown Face-Cap, Floyd A. Beckford, Alyssa Stott, P. Canisius Mbarushimana, Marc-Andre Leblanc, Kinsey Hall, Samantha Smith, Jimmie L. Bullock, Dennis J. Houghton, Alvin A. Holder, Nikolay Gerasimchuk, Antonio Gonzalez-Sarrías

Chemistry & Biochemistry Faculty Publications

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10 …

A Novel Copper (Ii) Complex Identified As A Potent Drug Against Colorectal And Breast Cancer Cells And As A Poison Inhibitor For Human Topoisomerase Iiᶐ, Shayna Sandhaus, Rosella Taylor, Tiffany Edwards, Alexis Huddleston, Stephen J. Beebe, Alvin A. Holder

Bioelectrics Publications

A novel complex, [Cu(acetylethTSC)Cl]Cl · 0.25C₂H₅OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIᶐ which may account for the observed anti-cancer effects.

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Synthesis Of Medicinally Relevant Thiazolyl Aryl Ketones Under Mild Conditions, Danielle M. Gardner

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose: The growing amount of clinical resistance observed in current antifungal drugs and in anti-HIV pharmaceuticals is a concern in the medical community. The purpose of this study is to develop a mild synthetic process for biomedically relevant thiazolyl aryl ketones that can be used to develop antifungal and anti-HIV drugs. We hypothesized that the proposed synthetic technique would be more efficient, produce fewer unwanted byproducts, and be more tolerant of functional groups than existing methods.

Methods: Prior to each of the ketone reactions, the necessary salt was synthesized by mixing thiazole and 9-bromofluorene neat in a reaction tube heated …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Microglial cells in the brains of Alzheimer's patients are known to be recruited to amyloid-beta (Aβ) plaques where they exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. In this study, we show that microglia stressed by exposure to sodium arsenite or Aβ(1–42) peptides or fibrils form ex- tensive stress granules (SGs) to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of SGs, is active within the resulting SGs and stimulates the production of reactive oxygen and nitrogen species that are toxic to neuronal cells. This sequestration of SYK inhibits the ability of microglial …

Formaldehyde From E-Cigarettes - It's Not As Simple As Some Suggest, James F. Pankow, Robert M. Strongin, David H. Peyton

Chemistry Faculty Publications and Presentations

The Authors address critics of a previously published letter to the Editor in The New England Journal of Medicine, pertaining to hidden formaldehyde in E-Cigarette aerosols and the need for future testing of their safety.

Electrochemical Characterization Of Protein Adsorption Onto Yngrt-Au And Vlgxe-Au Surfaces, Hanna Trzeciakiewicz, Jose Esteves-Villanueva, Rania Soudy, Kamaljit Kaur, Sanela Martic-Milne

Pharmacy Faculty Articles and Research

The adsorption of the proteins CD13, mucin and bovine serum albumin on VLGXE-Au and YNGRT-Au interfaces was monitored by electrochemical impedance spectroscopy in the presence of [Fe(CN)6]3−/4−. The hydrophobicity of the Au surface was tailored using specific peptides, blocking agents and diluents. The combination of blocking agents (ethanolamine or n-butylamine) and diluents (hexanethiol or 2-mercaptoethanol) was used to prepare various peptide-modified Au surfaces. Protein adsorption onto the peptide-Au surfaces modified with the combination of n-butylamine and hexanethiol produced a dramatic decrease in the charge transfer resistance, Rct, for all three proteins. In contrast, polar peptide-surfaces induced a minimal change in …

Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting …

Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polyrotaxanes are polymers that have macrocycles threaded onto them, analogous to beads threaded onto a string. These materials are used for a variety of different biomedical applications.^1-3 The Thompson group has been developing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) polyrotaxanes as therapeutics for the treatment of Niemann-Pick Type C (NPC) disease. NPC is a debilitating genetic disorder where cholesterol accumulates in the lysosomes of cells.⁴ Developing a scalable process is crucial for the advancement of these materials as NPC therapeutics. The goal of this project is to optimize the only protocol for the synthesis of HP-β-CD/Pluronic polyrotaxanes in order to develop a …

The Synthesis And Study Of The Biological And Colloidal Properties Of Bolaamphiphiles, Louis M. Damiano

Senior Honors Projects, 2010-2019

Over the past decade, antibiotic resistant bacteria have caused infections in patients throughout the world.^[1] The rise in antibiotic resistance is primarily due to the misuse and overuse of antibiotics. ^[1] To counter the increase in antibiotic resistance, infection control mechanisms have been aggressively researched in recent years. In particular, drug delivery has become a focal point to fight antibiotic resistant infections.^[2] Amphiphiles have a wide range of applications in the clinical setting, including the ability to inhibit bacterial transference because of their bactericidal activity. ^[3] Bolaamphiphiles are a subclass of amphiphiles that possess two or more hydrophilic …

Distributed Drug Discovery: Synthesis Of Unnatural Amino Acids As Potential Antimalarial Drugs, Amanda Dugan

Honors College

Through the collaboration of many institutions across the globe, the Distributed Drug Discovery project founded at Indiana University-Purdue University Indianapolis seeks to aid in the development of drugs for the developing world. In response to two antimalarial assay hits, our team at Abilene Christian University has synthesized many unnatural amino acid analogs using resin-based combinatorial chemistry. Proton nuclear magnetic resonance spectroscopy has been used to characterize the compounds and thin layer chromatography to determine purity. All compounds were purified on hypersep cyanosilica columns.

Flavour Chemicals In Electronic Cigarette Fluids, Peyton A. Tierney, Clarissa D. Karpinski, Jessica E. Brown, Wentai Luo, James F. Pankow

Chemistry Faculty Publications and Presentations

Background: Most e-cigarette liquids contain flavour chemicals. Flavour chemicals certified as safe for ingestion by the Flavor Extracts Manufacturers Association may not be safe for use in e-cigarettes. This study identified and measured flavour chemicals in 30 e-cigarette fluids.

Methods: Two brands of single-use e-cigarettes were selected and their fluids in multiple flavour types analysed by gas chromatography/mass spectrometry. For the same flavour types, and for selected confectionary flavours (eg, bubble gum and cotton candy), also analysed were convenience samples of e-cigarette fluids in refill bottles from local ‘vape’ shops and online retailers.

Results: In many liquids, total flavour chemicals …

Stability Of Lidocaine Tested By Forced Degradation And Its Interactions With Serum Albumin, Lindsay Nichols

STAR Program Research Presentations

A concern for future long-term manned space expeditions is the ability to treat illnesses with appropriate pharmaceuticals. However, pharmaceuticals degrade faster in space than on Earth presumably due to an abundance of space radiation. The stability of Lidocaine was investigated because it is a common pain reliever currently used on the International Space Station. One of the most common proteins in blood is serum albumin, which acts as a carrier to distribute drugs throughout the body. It is important to know how well the drug binds to serum albumin so that the rate of distribution of Lidocaine-bound protein in blood …

Development Of Non-Traditional Platinum Anticancer Agents: Trans-Platinum Planar Amine Compounds And Polynuclear Platinum Compounds, Daniel E. Lee

Theses and Dissertations

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds

By Daniel E. Lee, Ph.D.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2015

Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry

Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied …

Biginelli Synthesis And Characterization Of Potentially Anti-Proliferative Dihydropyrimidinone Thione Analogs, Timothy K. Summers

Theses and Dissertations

No abstract provided.

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie

Williams Honors College, Honors Research Projects

SMRT/HDAC Associated Repressor Protein interacts with the long noncoding RNA, produced by SRA, by binding at the RRMs. Three projects were done to prepare the truncated proteins for use in 2D and 3D NMR experiments. The first focuses on RRM 3 and its optimization during the purification process. The second focuses on RRM 2-4, which was found to be missing two alpha helices that may be important for protein stability. These helices can also interact with RRM 3 as well due to the tight association of RRMs 3 and 4. The two step PCR extension of RRM 2-4 was assumed …

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C² substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by ¹H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. …

Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger

College of Graduate Studies: Theses & Dissertations

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.

Predicting Aqueous Solubility Of Pharmaceutical Agents By Solid Dispersion Prepared By Solvent Evaporation Method, Karthik Reddy Patlolla

University of the Pacific Theses and Dissertations

Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble …

Curcumin: A Folklore Remedy From Kitchen On The Way To Clinic As Cancer Drug, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Numerous compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, …

Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino

Masters Theses, 2010-2019

The decline in the development of novel antimicrobials, combined with the misusage and over prescription of antibiotics, has contributed to the increasing prevalence of antimicrobial-resistant infections. Thus development of effective novel disinfectants could reduce the transmission of pathogens and decrease the risk of infection by antibiotic resistant organisms. The antimicrobial activity of amphiphiles, compounds with hydrophobic and hydrophilic regions, was first reported in 1935, and has influenced the synthesis of amphiphiles with variations in structure. In this study, three series of amphiphiles were synthesized by two subsequent Menshutkin reactions. Each amphiphile contains one or two hydrocarbon tails ranging from 8 …

Tuning Responsiveness Of Polypeptide Based Block Copolymers For Drug Delivery, Ashley J. Johnson

Dissertations

The goal of this dissertation was to tune the pH response and self-assembled morphologies of amphiphilic polypeptide block copolymers for use as drug delivery vehicles. Poly(L-lysine) and poly(L-glutamtic acid) are responsive, ionizable polypeptides that undergo secondary structure transitions, from α-helix to random coil, whereby the change in conformation of the peptide chain results in changes to the global morphology of a self-assembled system. The main focus of this work was to understand how changes in the polymer composition and the local environment can lead to control over the behavior of the overall system. First, the responsive behavior of poly(L-lysine) block …

Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, Kamaljit Kaur, Subir Bhattacharjee, Rajesh G. Pillai, Sahar Ahmed, Sarfuddin Azmi

Pharmacy Faculty Articles and Research

Naphthenic acids (NAs) are water-soluble components of petroleum. The characterization and quantification of NAs by analytical methods have proved quite challenging, whilst the toxic effects of these water-soluble compounds on a variety of organisms adversely affecting reproduction and steroid production is becoming apparent. In this study, we report a fluorescence-based competitive binding method for rapid sensing of the presence of NAs using cellulosic peptide array strips as sensors. The peptide array was designed from sequences derived from the estrogen receptor (ER). Several of these peptides were able to detect the presence of NAs at low micromolar (∼5 mg L^{−1 …}

Effect Of Sweeteners On The Renin-Angiotensin System In Rats, Jacob Ball

Journal of Undergraduate Research at Minnesota State University, Mankato

Normal abundant dietary sugars such as fructose and sucrose can contribute to hypertension and other health issues. To avoid these health complications, many individuals use artificial sweeteners. An equivalent intake of some artificial sweeteners also can lead to hypertension. However, Stevia, a sweetener that is isolated from a Paraguayan plant, was shown in relevant literature to decrease blood pressure in both rat specimens and humans. The general purpose of this research project was to study the effect of Stevia, saccharin, and sucrose on the expression of two key components of the renin-angiotensin- aldosterone system (RAAS): prorenin receptor (PRR) and angiotensin …