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Coumarins And P450s, Studies Reported To-Date, Maryam Foroozesh, Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu 2019 Xavier University of Louisiana

Coumarins And P450s, Studies Reported To-Date, Maryam Foroozesh, Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu

Faculty and Staff Publications

Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in themetabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.


Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins 2019 Otterbein University

Mechanistic Studies And Derivative Effects In 1, 3, 4- Oxadiazole Synthesis Via Cyclodehydration Reactions, Evan Huggins

Undergraduate Honors Thesis Projects

In the world of pharmaceutical synthesis, research to combat foreign pathogens is always necessary. Scientists have been exploring different methods in order to synthesize the most effective compounds in antibacterial, anticancer, anti-inflammatory, and many other treatments. A key component within these versatile compounds are 1,3,4-oxadiazoles. Current methods to synthesize these compounds are inefficient. This research seeks to improve oxadiazole synthesis; however, the mechanism of this reaction is unknown. The goal of this project was to study the mechanistic pathway in the discovered, one-pot cyclodehydration synthesis of 1,3,4-oxadiazoles. In the first part of this study, a diacylhydrazine intermediate was proposed. This …


The Effects Of Cannabidiol And Delta 9-Tetrahydrocannabinol Concentration On Breast Cancer Cells, Dorothy Agyemang 2019 University of Northern Colorado

The Effects Of Cannabidiol And Delta 9-Tetrahydrocannabinol Concentration On Breast Cancer Cells, Dorothy Agyemang

Ursidae: The Undergraduate Research Journal at the University of Northern Colorado

Delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids that have a potential impact on cancer treatments. Studies have shown that certain cannabinoids cause cancer cells to die, but only with the right concentration, which has not been well documented. The purpose of this study is to determine the exact concentration of CBD and THC needed to kill MCF-7 breast cancer cells. In this experiment, the initial treatment group will be treated with CBD or THC at concentrations of 0.1, 1, 10 and 100 micromolar. These concentrations were arbitrarily chosen because there is not an established baseline. Cell metabolic activity will …


Development Of Ruthenium Drugs As Anticancer Agents, Daniel Boy 2019 Taylor University

Development Of Ruthenium Drugs As Anticancer Agents, Daniel Boy

Chemistry & Biochemistry Student Projects

An overview of literature that outlines the research methods of the development of proposed Ruthenium based anti-cancer agents.


A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang 2019 Cleveland State University

A Quantitative Lc-Ms/Ms Method For Determination Of A Small Molecule Agonist Of Epha2 In Mouse Plasma And Brain Tissue, Bo Zhong, Yaxin Li, Nethrie Idippily, Aaron Petty, Bin Su Ph.D., Bingcheng Wang

Chemistry Faculty Publications

Compound 27 {1, 12‐bis[4‐(4‐amino‐6,7‐dimethoxyquinazolin‐2‐yl)piperazin‐1‐yl]dodecane‐1,12‐dione} is a novel small molecule agonist of EphA2 receptor tyrosine kinase. It showed much improved activity for the activation of EphA2 receptor compared with the parental compound doxazosin. To support further pharmacological and toxicological studies of the compound, a method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC–MS/MS) has been developed for the quantification of this compound. Liquid–liquid extraction was used to extract the compound from mouse plasma and brain tissue homogenate. Reverse‐phase chromatography with gradient elution was performed to separate compound 27 from the endogenous molecules in the matrix, followed by …


Analysis Of Drug–Protein Interactions During Diabetes By High-Performance Affinity Chromatography, Pingyang Tao 2019 University of Nebraska-Lincoln

Analysis Of Drug–Protein Interactions During Diabetes By High-Performance Affinity Chromatography, Pingyang Tao

Department of Chemistry: Dissertations, Theses, and Student Research

High-performance affinity chromatography (HPAC) is a type of liquid chromatography in which solutes are separated based on their binding to a stationary phase that is a biologically-related agent. Sulfonylurea drugs have significant binding to proteins in blood, with most of this binding is believed to occur with human serum albumin (HSA). HSA is known to be modified as a result of the high serum levels of glucose that is present during diabetes, which may also alter the function of HSA as a binding agent for many drugs in circulation. Some modifications of HSA that can occur during diabetes involves early …


An Improved Synthesis Of Adefovir And Related Analogues, Timothy P. O'Sullivan, et al 2019 Department of Physical Sciences, Cork Institute of Technology, Cork, Ireland

An Improved Synthesis Of Adefovir And Related Analogues, Timothy P. O'Sullivan, Et Al

Physical Sciences Publications

An improved synthesis of the antiviral drug adefovir is presented. Problems associated with current routes to adefovir include capricious yields and a reliance on problematic reagents and solvents, such as magnesium tert-butoxide and DMF, to achieve high conversions to the target. A systematic study within our laboratory led to the identification of an iodide reagent which affords higher yields than previous approaches and allows for reactions to be conducted up to 10 g in scale under milder conditions. The use of a novel tetrabutylammonium salt of adenine facilitates alkylations in solvents other than DMF. Additionally, we have investigated how …


Lew.1wr1 Rats Have Altered Inflammation Responses During Type 1 Diabetes Induction, Madushika Wimalarathne, Kayleigh Cantrell, Joshua Derbort 2019 University of Alabama in Huntsville

Lew.1wr1 Rats Have Altered Inflammation Responses During Type 1 Diabetes Induction, Madushika Wimalarathne, Kayleigh Cantrell, Joshua Derbort

Research Horizons Day Posters

No abstract provided.


Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu 2019 Cleveland State University

Tracking Decitabine Incorporation Into Malignant Myeloid Cell Dna In Vitro And In Vivo By Lc-Ms/Ms With Enzymatic Digestion, Sujatha Chilakala, Ye Feng, Lan Li, Reda Mahfouz, Ebrahem Quteba, Yogen Saunthararajah, Yan Xu

Chemistry Faculty Publications

The DNA hypomethylating agents decitabine and 5-azacytidine are the only two drugs approved for treatment of all subtypes of the myeloid malignancy myelodysplastic syndromes (MDS). The key to drug activity is incorporation into target cell DNA, however, a practical method to measure this incorporation is un-available. Here, we report a sensitive and specific LC-MS/MS method to simultaneously measure decitabine incorporation and DNA hypomethylation. A stable heavy isotope of 2'-deoxycytidine was used as an internal standard and one-step multi-enzyme digestion was used to release the DNA bound drug. Enzyme-released decitabine along with other mononucleosides were separated by a reverse-phase C-18 column …


Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed 2019 Chapman University

Purification And Characterization Of A Nonspecific Lipid Transfer Protein 1 (Nsltp1) From Ajwain (Trachyspermum Ammi) Seeds, Meshal Nazeer, Humera Waheed, Maria Saeed, Saman Yousuf Ali, M. Iqbal Choudhary, Zaheer Ul-Haq, Aftab Ahmed

Pharmacy Faculty Articles and Research

Ajwain (Trachyspermum ammi) belongs to the family Umbelliferae, is commonly used in traditional, and folk medicine due to its carminative, stimulant, antiseptic, diuretic, antihypertensive, and hepatoprotective activities. Non-specific lipid transfer proteins (nsLTPs) reported from various plants are known to be involved in transferring lipids between membranes and in plants defense response. Here, we describe the complete primary structure of a monomeric non-specific lipid transfer protein 1 (nsLTP1), with molecular weight of 9.66 kDa, from ajwain seeds. The nsLTP1 has been purified by combination of chromatographic techniques, and further characterized by mass spectrometry, and Edman degradation. The ajwain nsLTP1 …


Synthesis Of A Sulfur Variant For Treatment Of Trypanosomiasis, Carlos Vera-Esquivel 2019 University of Nebraska at Omaha

Synthesis Of A Sulfur Variant For Treatment Of Trypanosomiasis, Carlos Vera-Esquivel

UNO Student Research and Creative Activity Fair

Previous work in our lab has found diphenyl ether benzylamines showed a successful response with a micromolar concentration of our lead compound to treat the deadly Trypanosamiosis rhodesience. Furthermore, mammalian cell lines saw promising resistance towards damages. The goal of this study was to synthesize a diphenyl thio benzylamine variant. This variant was more active toward T. b. rhodesience but showed more toxicity to both rat 10 (IC50 mM) and human cell lines (HFF, HC-04, U-2 OS, and HEK293). The selectivity index (ratio of toxicity to activity in the same concentration units (SI)) …


Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas 2019 CSIR· National Chemical Laboratory

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase …


Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang 2019 CUNY Graduate Center

Bisthioether Stapled Peptides Targeting Polycomb Repressive Complex 2 Gene Repression, Gan Zhang

Dissertations, Theses, and Capstone Projects

Interactions between proteins play a key role in nearly all cellular process, and therefore, disruption of such interactions may lead to many different types of cellular dysfunctions. Hence, pathologic protein-protein interactions (PPIs) constitute highly attractive drug targets and hold great potential for developing novel therapeutic agents for the treatment of incurable human diseases. Unfortunately, the identification of PPI inhibitors is an extremely challenging task, since traditionally used small molecule ligands are mostly unable to cover and anchor on the extensive flat surfaces that define those binary protein complexes. In contrast, large biomolecules such as proteins or peptides are ideal fits …


An Overview Of Capillary Electrophoresis (Ce) In Clinical Analysis, David S. Hage 2019 University of Nebraska-Lincoln

An Overview Of Capillary Electrophoresis (Ce) In Clinical Analysis, David S. Hage

David Hage Publications

The development and general applications of capillary electrophoresis (CE) in the field of clinical chemistry are discussed. It is shown how the early development of electrophoresis was closely linked to clinical testing. The rise of gel electrophoresis in clinical chemistry is described, as well as the eventual developments that lead to the creation and the use of modern CE. The general principles of CE are reviewed and the potential advantages of this method in clinical testing are examined. Finally, an overview is presented of several areas in which CE has been developed and is currently being explored for use with …


Isolation And Identification Of Hsc70 Conjugates In Raw264.7 Murine Macrophage-Like Cells, Michael Arland Parsons 2019 Marshall University

Isolation And Identification Of Hsc70 Conjugates In Raw264.7 Murine Macrophage-Like Cells, Michael Arland Parsons

Theses, Dissertations and Capstones

IL12R- β2 is a Type I cytokine receptor and contains the WXXW (WSNWS) sequence that often predicates the post-translational addition of mannose to a tryptophan residue via a carbon-carbon bond. This study will stimulate expression of IL12R- β2 in RAW 264.7 Macrophage-Like Cells by shutting down the extracellular signal kinase (ERK) pathway and introducing inflammatory agents lipopolysaccharide and CpG DNA in order to collect a concentrated sample of IL12R- β2. These samples will be analyzed for the presence of C-mannosyltryptophan residue


Role Of Water On The Rotational Dynamics Of The Organic Methylammonium Cation: A First Principles Analysis, Ross D. Hoehn, Joseph S. Francisco, Sabre Kais, Ali Kachmar 2019 Purdue University

Role Of Water On The Rotational Dynamics Of The Organic Methylammonium Cation: A First Principles Analysis, Ross D. Hoehn, Joseph S. Francisco, Sabre Kais, Ali Kachmar

Department of Chemistry: Faculty Publications

Understanding the degradation mechanisms of lead-halide perovskites (CH3NH3PbI3) under exposure to liquid/aerosol water is an essential problem within the photovoltaic community. Herein we investigate both the static and the dynamic properties of the methylammonuim cation (MA) as it coordinates with invading water molecules (MA.(H2O)n, n = 1, 2, 3, 4) using both stationary state quantum mechanics and first principle molecular dynamics simulations. Various solvation structures of MA were characterized by their stabilization energies, dipoles, and Maximally-Localized Wannier Function (MLWF) centers. Calculation – and analysis – of vibrational shifts in the …


Structural Basis Of 7sk Rna 5′ Γ-Phosphate Methylation And Retention By Mepce, Yuan Yang, Catherine D. Eichhorn, Yaqiang Wang, Duilio Cascio, Juli Feigon 2019 UCLA

Structural Basis Of 7sk Rna 5′ Γ-Phosphate Methylation And Retention By Mepce, Yuan Yang, Catherine D. Eichhorn, Yaqiang Wang, Duilio Cascio, Juli Feigon

Department of Chemistry: Faculty Publications

Among RNA 5′-cap structures, γ-phosphate monomethylation is unique to a small subset of noncoding RNAs, 7SK and U6 in humans. 7SK is capped by methylphosphate capping enzyme (MePCE), which has a second non-enzymatic role as a core component of the 7SK RNP that is an essential regulator of RNA transcription. We report 2.0 and 2.1 Å X-ray crystal structures of human MePCE methyltransferase domain bound to S-adenosylhomocysteine (SAH) and uncapped or capped 7SK substrates, respectively. 7SK recognition is achieved by protein contacts to a 5′ hairpin-single-stranded RNA region, explaining MePCE specificity for 7SK and U6. The structures reveal SAH and …


Molecular Insights Into Cage Occupancy Of Hydrogen Hydrate: A Computational Study, Rui Ma, Hong Zhong, Jinxiang Liu, Jie Zhong, Youguo Yan, Jun Zhang, Jiafang Xu 2019 China University of Petroleum

Molecular Insights Into Cage Occupancy Of Hydrogen Hydrate: A Computational Study, Rui Ma, Hong Zhong, Jinxiang Liu, Jie Zhong, Youguo Yan, Jun Zhang, Jiafang Xu

Department of Chemistry: Faculty Publications

Density functional theory calculations and molecular dynamics simulations were performed to investigate the hydrogen storage capacity in the sII hydrate. Calculation results show that the optimum hydrogen storage capacity is ~5.6 wt%, with the double occupancy in the small cage and quintuple occupancy in the large cage. Molecular dynamics simulations indicate that these multiple occupied hydrogen hydrates can occur at mild conditions, and their stability will be further enhanced by increasing the pressure or decreasing the temperature. Our work highlights that the hydrate is a promising material for storing hydrogen.


Brush-Arm Star Polymer Imaging Agents And Uses Thereof, Jeremiah A. Johnson, Hung Vanthanh Nguyen, Andrzej Rajca 2019 Boston, MA

Brush-Arm Star Polymer Imaging Agents And Uses Thereof, Jeremiah A. Johnson, Hung Vanthanh Nguyen, Andrzej Rajca

Department of Chemistry: Faculty Publications

Disclosed are methods, compositions, reagents, systems, and kits to prepare nitroxide-functionalized brush-arm star polymer organic radical contrast agent (BASP-ORCA) as well as compositions and uses thereof. Various embodiments show that BASP-ORCA display unprecedented per-nitrox-ide and per-molecule transverse relaxivities for organic radical contrast agents, exceptional stability, high water solubility, low in vitro and in vivo toxicity, and long blood compartment half-life. These materials have the potential to be adopted for tumor imaging using clinical high-field 1H MRI techniques.


Growth Of Carbon Dioxide Whiskers, Avinash Kumar Both, Chin Li Cheung 2019 University of Nebraska - Lincoln

Growth Of Carbon Dioxide Whiskers, Avinash Kumar Both, Chin Li Cheung

Department of Chemistry: Faculty Publications

We report the growth of carbon dioxide (CO2) whiskers at low temperatures (–70 °C to –65 °C) and moderate pressure (4.4 to 1.0 bar). Their axial growth was assessed by optical video analysis. The identities of these whiskers were confirmed as CO2 solids by Raman spectroscopy. A vapor– solid growth mechanism was proposed based on the influence of the relative humidity on the growth.


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