Digital Commons Network^™

The Effects Of Passive Integrated Transponder Tagging On Cortisol Release In The Gulf Killifish, Fundulus Grandis, Ariel Marcelo Hernandez

Senior Honors Theses

Due to its ease of use, low cost, and essentially limitless number of unique codes, PIT tagging has become the favored technique for tagging individuals in biological studies. However, studies employing PIT tagging generally assume that stress due to the implantation and presence of a PIT tag has no influence on the experimental results. This study investigated the effects of PIT tagging on levels of the stress hormone cortisol in the Gulf Killifish, Fundulus grandis, an estuarine fish of the Gulf of Mexico that is prone to daily or seasonal environmental stressors. Cortisol was measured non-invasively by extracting and …

Photoremovable Protecting Groups Based On Electrocyclization With Leaving Group Expulsion Via A Proposed Zwitterion, Gilbert Ndzeidze

Dissertations (1934 -)

The triplet excited state of thioxanthone produced by photolysis undergoes reversible triplet energy transfer with a trimethylene - linked benzothiophene-2-carboxanilide ring system. The ensuing electrocyclic ring closure of the anilide moiety produces a putative zwitterionic intermediate that is capable of expelling leaving groups (LG-) from the C-3 position of the benzothiophene ring. Stern-Volmer quenching studies with cyclohexadiene as quencher furnish the rate constants for the triplet excitation transfer in the forward and reverse directions, which can be expressed as an equilibrium constant K = 0.058. Overall, the rate of triplet excited state reaction becomes K x kr = 5.7 x …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, Michael P. D'Erasmo

Dissertations, Theses, and Capstone Projects

Historically, natural products have provided unique research opportunities and challenges for organic synthesis, chemical biology, and medicinal chemistry due to their molecular complexity and effects on physiological systems. The total synthesis of natural products has not only produced novel reaction methods and strategies capable of efficiently generating complex structural motifs but also granted access to sufficient quantities of otherwise scarce natural product material for clinical evaluation. These synthetic efforts have facilitated the formation of a transdisciplinary partnership between chemistry, biology, and medicine that has been paramount in elucidating the chemical and pharmaceutical utility of natural products. Chapter I of this …

Synthesis And Biological Evaluation Of Small Molecular Drug Candidates For The Treatment Of Her2 Overexpressed Breast Cancer, Anran Zhao

ETD Archive

In the US breast cancer is the most common cancer after skin cancer. Currently in the US the average risk of a woman to develop breast cancer in her life is roughly 12%. About 25-30% of breast cancer patients have HER2 overexpressed tumor, and the growth of tumor cell is depend on HER2 pathway. It has been well-documented that patients with over-expressed HER2 are associated with increased disease recurrence, worse prognosis and lower survival. Currently there are two type of HER2 targeting drug. The first group is HER2 monoclonal antibody drugs such as trastuzumab approved by FDA in 1998; the …

Design And Synthesis Of Oligo-(3,5-Dithio-Β-D-Glucopyranoside) As Β-(1→3)-Glucan Mimetics, Xiaoxiao Liao

Wayne State University Dissertations

This dissertation presents the design and synthesis of oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics. The synthesized dimeric, trimeric and tetrameric mimetics were tested for their binding affinities to Dectin-1 and CR3 and their abilities to activate phagocytosis and pinocytosis.

The first chapter gives an introduction of β-(1 → 3)-D-glucan. It gives an introduction about the structure and origin of β-(1 → 3)-D-glucan as well as the immunostimulating effect of natural β-(1 → 3)-D-glucan. The study of interaction between β-(1 → 3)-D-glucan and the receptors leads to a conclusion that the hydrophobicity of β-(1 → 3)-D-glucan is crucial to its immunostimulating …

Biological Study On Novel Coumarinyl 1,3,4-Oxadiazoles, Maja Molnar, Ana Amic, Valentina Pavic, Tihomir Kovac, Marija Kovac, Elizabeta Has-Schön

Turkish Journal of Chemistry

Coumarinyl 1,3,4-oxadiazoles were synthesized from Schiff bases and acetic anhydride. All compounds were characterized by melting points and their structures confirmed by mass and $^{1}$H and $^{13}$C NMR spectrometry. These novel coumarinyl derivatives were subjected to antibacterial, antifungal, anta atoxigenic, and antioxidant activity. Their activity varied depending on their structure, where 2-(3-acetyl-5-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)- 2,3-dihydro-1,3,4-oxadiazol-2-yl)-1,4-phenylene diacetate showed significant antioxidant and antibacterial activity on B. subtilis. 4-(3-Acetyl-5-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-2,3-dihydro-1,3,4-oxadiazol-2-yl)-1,2-phenylene diacetate was found to possess excellent antifungal and antia atoxigenic activity.

Synthesis And Evaluation Of Novel 1,3,4-Thiadiazole--Fluoroquinolone Hybrids As Antibacterial, Antituberculosis, And Anticancer Agents, Asli Demi̇rci̇, Kaan Gökçe Karayel, Esra Tatar, Si̇nem Öktem Okullu, Ni̇han Ünübol, Paki̇ze Nesli̇han Taşli, Zühtü Tanil Kocagöz, Fi̇kretti̇n Şahi̇n, İlkay Küçükgüzel

Turkish Journal of Chemistry

A series of 5-substituted-1,3,4-thiadiazole-based fluoroquinolone derivatives were designed as potential antibacterial and anticancer agents using a molecular hybridization approach. The target compounds 16-25 were synthesized by reacting the corresponding $N$-(5-substituted-1,3,4-thiadiazol-2-yl)-2-chloroacetamides with ciprofloxacin or norfloxacin. The purity and identity of the synthesized compounds were determined by the use of chromatographic and spectral techniques (NMR, IR, MS, etc.) besides elemental analysis. Antibacterial, antituberculosis, and anticancer activity of the target compounds were evaluated against selected strains and cancer cell lines. Compound 20 was appreciated as the most active agent representing antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC values of 4 …

Progress Toward Controlled Disulfide Formation To Access Neuroactive Conotoxins, Thilini Kondasinghe

Wayne State University Dissertations

"Conotoxins are mini proteins isolated from marine snails of the Conus family. They have shown activity in the selective inhibition of various ion channels. Therefore, they present an opportunity as possible therapy for a myriad of neurological ailments. The synthesis of conotoxins would enable both biological studies and evaluation of these structures as lead targets for therapeutics. However, establishing a reliable method to consistently folding disulfide rich proteins, including conotoxin, into their native structure has been challenging over few decades. In this research project, it is shown the progress towards a mild, efficient, and broadly applicable methods to generate the …

Synthesis And Application Of Photoreactive Collagen Peptides, And Antiparasitic Agents, Alfredo Ornelas

Open Access Theses & Dissertations

Since the introduction of solid phase peptide synThesis in 1963, peptides and post-translationally modified peptides can be conveniently synthesized in the chemistry laboratory. In the past decade, there has been a remarkable increase in bioactive peptide research and the therapeutic peptide market value is expected to hit $25 billion this year. Peptides can also provide structural and biological functions and have emerged as promising novel biomaterials in tissue engineering. Here we will describe three different projects, which deal with different aspects of peptide chemistry, i.e. synthetic method development, exploration of new peptide biomaterials, and the use of cell penetrating peptides …

Quantitation Without Calibration: Response Profile As An Indicator Of Target Amount, Mrittika Debnath

Graduate Research Theses & Dissertations

Quantitative assessment of biomarkers is essential in numerous contexts from decision-making in clinical situations to food quality monitoring to the interpretation of life-science research findings. However, appropriate quantitation techniques are not as widely addressed as detection methods. One of the major challenges in biomarker’s quantitation is the need to have a calibration for correlating a measured signal to a target amount. The step complicates the methodologies and makes them less sustainable. In this work, we addressed the issue via a new strategy: relying on the position of response profile rather than absolute signal for assessment of a target nucleic acid’s …

The Great Potential Of Redox Active Ligands: Applications In Cancer Research And Redox Active Catalysis, Meredith Miles

Browse all Theses and Dissertations

Metal N-heterocyclic carbene (NHC) complexes have recently gained much popularity due to their tunable, steric, and electronic properties. Applications for such versatile molecules include organocatalysis, olefin metathesis, sundry cyclization reactions, and materials chemistry. Redox active NHCs are of special interest due to their ability to alter the electronic properties of the metal centers they are ligated to. In the first chapter, Au(I)-NHC complexes were synthesized and tested for biological activity in human cancer cell lines. Increasing reactive oxygen species (ROS) in cellular systems has proven to be a successful pathway for treating cancer. The redox active group in this case …

Crystallographically Defined Silicon Macropore Membranes, Shannon C. Knight, Bret A. Unger, Kurt W. Kolasinski

Chemistry Faculty Publications

Laser ablation with nanosecond-pulsed Nd:YAG laser irradiation combined with anisotropic alkaline etching of Si wafers creates 4–20 µm macropores that extend all the way through the wafer. The walls of these macropores are crystallographically defined by the interaction of the anisotropy of the etchant with the orientation of the single-crystal silicon substrate: rectangular/octagonal on Si(001), parallelepiped on Si(110), triangular/hexagonal on Si(111). Laser ablation can create pillars with peak-tovalley heights of over 100 µm. However, with nanosecondpulsed irradiation at 532 nm, the majority of this height is created by growth above the original plane of the substrate whereas for 355 nm …

Syntheses Of Azepinoindole Alkaloids Cimitrypazepine, Fargesine And Hyrtioreticulins C & D, Ganesh Ghimire

Graduate Theses, Dissertations, and Problem Reports (ETD)

The Watanabe-Cenini-Söderberg reductive N-heterocyclization has emerged as a powerful tool for the synthesis of a variety of functionalized indoles. Söderberg’s elaboration of this methodology has been utilized as a late-stage cyclization protocol for the synthesis of azepinoindole alkaloids, a class of natural products characterized by an azepane skeleton fused with an indole ring. Short syntheses of the naturally occurring azepino[5,4,3-cd]indole alkaloids, cimitrypazepine, fargesine, and the diastereomeric hyrtioreticulins C & D have been completed starting from commercially available tetra-substituted benzene derivatives. The key azepinoindole core in each case was assembled via an intramolecular Mizoroki-Heck reaction followed by a …

Theoretical Circular Dichroism Spectra Of The Α-Helical Protein Calexitin With The Dipole Interaction Model Including The N-Π* Transition, Akongnwi C. Jungong, Tsvetan Aleksandrov, Rahul Nori, Justin Erickson, Kathryn A. Thomasson, Igor V. Uporov, Ethan R. Austhof, Emily Holt, Felix N. Ngassa

Chemistry Faculty Publications

Circular dichroism (CD) is an important structural biology technique used to study protein dynamics, and most especially the secondary structure of peptides and proteins. Although CD is a technique that is relatively easy to introduce to undergraduate students, the high cost of obtaining a conventional CD instrument and the time required for sample preparation prevents a good number of students from having hands-on experiments demonstrating the principle of CD. Herein, theoretical circular dichroism with the dipole interaction model, DInaMo, is proposed as a tool for introducing students to CD. Using the dipole interaction model, the CD spectra of an α-helical …

Multi-Dimensional Mass Spectrometry For The Characterization Of Glycopolymers, Maria Ganios

Williams Honors College, Honors Research Projects

Several glycopolymers synthesized by Activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP), were characterized by mass spectrometry to elucidate their microstructure and architecture. Analyses were performed using Matrix Assisted Laser Desorption Ionization- Time of Flight/ Time of Flight (MALDI-ToF/ToF) and Electrospray Ionization Mass Spectrometry (ESI-MS) instruments. The linear isopropylidenated glycopolymer (P65B1) analyzed with ESI-MS also was examined with multi-stage mass spectrometry (MSⁿ) using collision induced dissociation (CID) to examine the tetramer parent ion. This glycopolymer was found to be either cyclic or linear (sans end groups) due to the data being fit for both forms …

Split Aptameric Turn-On Fluorescence Sensor For Detection Of Sequence Specific Nucleic Acid At Ambient Temperature, Nanami Kikuchi

Electronic Theses and Dissertations

Nucleic acid amplification tests (NAATs) enable sensitive detection of low density infections that microscopy and rapid diagnostic test are not capable of detecting. They enable quantitative and qualitative nucleic acid detection, genotype analysis, and single nucleotide polymorphism (SNP) detection. Current state of the art molecular probes used with NAATs includes molecular beacon (MB), Taqman and its variations. This work presents novel molecular probe designed from Spinach and Dapoxyl aptamers. The aptamers are split into two parts (split aptamer), allowing greater sensitivity and selectivity towards fully complementary nucleic acid analyte. The major advantage of split aptamer probe over state-of-the-art fluorescent probes …

Synthesis Of Heterocycles Through Beta Lactams Ring Rupture, Bimal K. Banik

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

Many Beta lactams are widely used as medicines. The 4-membered ring present in the beta lactams is under strain and therefore, it can undergo cleavage reactions to diverse compounds. Chemical manipulation of the resulting products affords numerous molecules of interest. In this perspective, some examples developed at our laboratory are discussed

Versatile Catalytic Transfer Hydrogenations In Organic Synthesis, Bimal K. Banik, Khaled J. Barakat, Maghar S. Manhas

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

Catalytic transfer hydrogenation reactions are extremely useful in organic synthesis. We have investigated numerous reactions with ammonium formate (and other hydrogen gas donor) and 10% Pd/C successfully without using hydrogen gas. The reactions are very fast and produced products with high yields. Reduction of unsaturated groups, hydrogenolysis, reductive bond cleavage, allylic deacetoxylation, and dehalogenation are conducted using this method. In some instances, useful selectivity of reactions is observed. Most of the reactions are investigated with β-lactams as the substrates.

Stereoselectivity Of Phthalimido Β-Lactams Formation: Synthesis Of 3-Amino Β-Lactams Through A Facile Deprotection Reaction, Armando Paniagua, Ram Naresh Yadav, Sunena Chandra, Bimal K. Banik

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

Synthesis of amino β-lactams is a crucial objective because of the medicinal properties associated with them and the products derived from of them. Stereocontrolled synthesis of phthalimido β-lactams is performed and cis and trans-phthalimido β-lactams are deprotected with ethylene diamine (and other reagents) to amino β-lactams of diverse structures in excellent yield. This reaction is also conducted under solventless conditions to afford identical products.

Metastable-State Nh Photoacids And Organic Photo Carbon Monoxide Releasing Materials, Aluthwatte Rallage Nawodi Madhusanka Abeyrathna

Theses and Dissertations

The recently discovered metastable-state photoacids (mPAHs) can produce a large proton concentration with high efficiency and good reversibility upon irradiation with visible light with moderate intensity. Therefore, mPAHs can be conveniently incorporated in to different systems to control various proton-transfer processes. Recently, several applications of mPAHs have been demonstrated. However, none of the previously reported mPAHs can function at a pH 7.4. Thus, biological applications of mPAHs are limited. In this work, mPAHs that can reversibly release a proton in PBS buffer (pH = 7.4) under visible light are designed and synthesized. NH-PAH-1 is the first of this type of …

Synthesis, Characterization And Application Of Sugar-Based Low Molecular Weight Gelators, Ifeanyi Simeon Okafor

Chemistry & Biochemistry Theses & Dissertations

Low molecular weight gelators (LMWGs) are an interesting class of compound that have gained considerable attention especially because of their potential applications for soft biomaterials. Carbohydrate based low molecular weight hydrogelators and organogelators are able to selfassemble and form ordered supramolecular structures, which are useful for exploring biomedical applications. The resulting gelators are responsive to external stimuli because of the weak noncovalent intermolecular forces and interaction that influences self-assembly. Stimuli-responsive supramolecular organogels with interesting properties in response to external environmental stimuli have gained considerable attention due to their applications in biomaterials, sensors and for drug delivery.

One of the major …

Toxicant Formation In Dabbing: The Terpene Story, Jiries Meehan-Attrash, Wentai Luo, Robert M. Strongin

Chemistry Faculty Publications and Presentations

Inhalable, noncombustible cannabis products are playing a central role in the expansion of the medical and recreational use of cannabis. In particular, the practice of “dabbing” with butane hash oil has emerged with great popularity in states that have legalized cannabis. Despite their growing popularity, the degradation product profiles of these new products have not been extensively investigated. The study herein focuses on the chemistry of myrcene and other common terpenes found in cannabis extracts. Methacrolein, benzene, and several other products of concern to human health were formed under the conditions that simulated realworld dabbing. The terpene degradation products observed …

Synthesis Of Small Molecule Heterocycles As Antimicrobial And Anticancer Agents, Zakeyah Ali Alsharif

Student Theses and Dissertations

This thesis contains three chapters. In chapter one, the synthesis of dihydropyrido-pyrimidones derivatives by using hexafluoroisopropanol (HFIP) as a solvent was reported and the synthesized compounds were tested against different bacteria but no activity was observed. In the second chapter, the syntheses of thiazoline and thiazole derivatives were reported. In this methodology, HFIP was used to promote for the reaction and sixty new molecules were synthesized. Two of these compounds showed promising activity as a potent anti-cancer agent against several cell lines. In the third chapter, pyrazole derivatives were synthesized and tested against different types of bacteria. Among these compounds, …

Review: New Frontiers In Metabolomics: From Measurement To Insight, Eli Riekeberg, Robert Powers

Robert Powers Publications

Metabolomics is the newest addition to the “omics” disciplines and has shown rapid growth in its application to human health research because of fundamental advancements in measurement and analysis techniques. Metabolomics has unique and proven advantages in systems biology and biomarker discovery. The next generation of analysis techniques promises even richer and more complete analysis capabilities that will enable earlier clinical diagnosis, drug refinement, and personalized medicine. A review of current advancements in methodologies and statistical analysis that are enhancing and improving the performance of metabolomics is presented along with highlights of some recent successful applications.

Design And Synthesis Of Selective Estrogen Receptor Β Agonists And Their Pharmacology, K. L. Iresha Sampathi Perera

Dissertations (1934 -)

Estrogens (17β-estradiol, E2) have garnered considerable attention in influencing cognitive process in relation to phases of the menstrual cycle, aging and menopausal symptoms. However, hormone replacement therapy can have deleterious effects leading to breast and endometrial cancer, predominantly mediated by estrogen receptor-alpha (ERα) the major isoform present in the mammary gland and uterus. Further evidence supports a dominant role of estrogen receptor-beta (ERβ) for improved cognitive effects such as enhanced hippocampal signaling and memory consolidation via estrogen activated signaling cascades. Creation of the ERβ selective ligands is challenging due to high structural similarity of both receptors. Thus far, several ERβ …

Novel Spectroscopic Tools To Differentiate Drug-Dna Binding Interactions, Fadwa Dhafer Hamad

Masters Theses

DNA-drug interactions play a major role in therapeutics, diagnostics, forensics and imaging. Drugs bind to DNA in several ways based on the mode of interaction and they alter protein-DNA interactions or breaks/cleaves DNA that can lead to the cure of the disease. The major goal of the research carried out in this thesis is to develop novel optical spectroscopic tools that can differentiate Drug-DNA binding interactions mode whether its intercalation or minor-groove binding. To achieve this goal, we developed two-photon absorption (2PA) cross-section based technique to differentiate between Drug-DNA binding modes. The investigations were carried out on two drug molecules, …

Stereochemical Preference Toward Oncotarget: Design Synthesis And In Vitro Anticancer Evaluation Of Diastereomeric B-Lactams, Fabian Olazarán-Santibáñez, Debasish Bandyopadhyay, Pilar Carranza-Rosales, Gildardo Rivera, Isias Balderas-Rentería

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

Purpose: In the battle against cancer discovery of new and novel chemotherapeutic agent demands extreme obligation. Development of anticancer compounds with higher potency and reduced side-effects is timely and challenging.

Experimental Design: A small series of fourteen diastereomeric β-lactams (seven pairs) were synthesized through multi-step process exploring [2+2] ketene-imine cycloaddition as the key step. Comparative stereochemical preferences were studied through computational docking and validated by in vitro evaluation. β-tubulin was considered as possible molecular target and in vitro anticancer evaluation was conducted against SiHa, B16F10, K562 and Chang cell lines. Caspase-3 activation assay and hematoxylin/eosin staining of the cells were …

Development Of New Routes For The Synthesis Of Carbaporphyrins And Carbachlorins, Navneet Sahota

Theses and Dissertations

Carbaporphyrins and carbachlorins are porphyrin analogs in which one of the nitrogens is replaced with a carbon atom within a porphyrin-like cavity. These systems form stable organometallic derivatives and exhibit unusual chemical reactivity. In the monocarbaporphyrinoids such as benzocarbaporphyrins, one of the pyrrole rings is replaced by an indene unit. Although syntheses of monocarbaporphyrins with fused rings have been widely investigated over the past 20 years, a few examples of carbaporphyrins without fused rings have been reported in the literature.

In this thesis, two projects were conducted to further explore carbaporphyrin and carbachlorin chemistry. The first project utilized a ‘3+1’ …