Polycyclic Compounds Commons^™

Phytochemical And In-Vitro Cytotoxic Analyses Of Flavonoid Species Isolated From Chromolaena Leivensis, Luke A. Bryant

Electronic Theses and Dissertations

As a leading cause of death worldwide, cancer and its treatments remain a primary source of interest among researchers. Modern studies are looking into bioselective cytotoxicity to create new chemotherapies that do not have the same harsh side effects as those we use today. Natural product research has a promising future for the development of such treatments. Specifically, polar flavonoids may be the key to a bioselective treatment. Such flavonoid species are native to plants, often within flower petals or within the body. A natural antioxidant, they are designed not to harm healthy cells. This study focuses on the plant …

Quantifying Black Carbon Concentrations In Georgia And Analyzing Associated Public Health Risks, Khloe R. Osborne

Honors Theses

Quantifying Black Carbon Concentrations in Georgia and Analyzing Associated Public Health Risks

One of the most daunting challenges of the industrial world is air pollution. Within this broad spectrum, there is an inhalable particle group named PM2.5, which contains black carbon. Black carbon has evidence that supports the generation and worsening of adverse health impacts, which may include birth complications, cognitive deficits in children, pulmonary aggravation, asthma, cardiovascular issues, neurological degenerative patterns, and cancer risk. This is especially seen in vulnerable populations, like children, elderly, and those who already suffer from weakened health, many of which reside in the southern …

The Influence Of Fermentation Duration And Secondary Fermentation Conditions On The Bioactive Compound Profile Of Kombucha, Jordan Vereen

Honors Theses

Kombucha is a fermented sweet tea produced using a symbiotic culture of bacteria and yeast (SCOBY) and has gained widespread popularity due to its proposed health benefits. Kombucha has been studied to understand these advantages in cardiovascular support, improved metabolism, increased antioxidant effects, enhanced antimicrobial properties, and even potentially slowing the progression of certain diseases. Despite its increasing popularity, the way in which the specific bioactive compounds responsible for these effects and the fermentation conditions that influence their production remain unclear. The present study, conducted in collaboration with Dr. Budner, focuses on quantifying bioactive compounds in kombucha to better understand …

Neurodevelopmental Effects Associated With In Utero Exposure To Bpa, Maximilian A. Nilsen, Grace A. Carlucci, Cody V. Thompson, Berfin Gul

Student Work

No abstract provided.

Development Of Tunable Rose Bengal Based-Nanogumbos As Potential Selective Chemotherapeutic Agents, William J.A. Russell

Honors College Theses

As cancer remains one of the greatest threats to the global population, the development of chemotherapeutic agents that are selective and tunable is of critical importance. Herein, a series of Rose Bengal (RB)-based GUMBOS, a group of uniform materials based on organic salts, were synthesized via counterion exchange between [Na]₂[RB] and three organic cations: tetrabutylphosphonium bromide [TBP][Br], tetraphenylphosphonium chloride [TPP][Cl], and 1-dodecyl-3-methylimidazolium chloride [C₁₂MIm][Cl]. The resulting GUMBOS were characterized through FT-IR, ESI-MS, NMR, and UV-Vis Spectroscopy. Partition coefficient studies indicated all GUMBOS exhibited hydrophobic physiochemical characteristics. These hydrophobic RB-based GUMBOS …

Proteomic Analysis Of Central Amygdala Systems Regulated By Mifepristone In The Context Of Alcohol Dependence, Stephanie S. Lee, Laura Monteagudo Romero, John W. Lammons, Jennifer M. Klein, Kimberly N. Edwards, Jessie J. Guidry, Scott Edwards

School of Graduate Studies Faculty Publications

Alcohol use disorder (AUD) is a psychiatric disorder characterized by escalated alcohol use and the emergence of negative affective symptoms. Studies have described a dysregulation of glucocorticoid receptor (GR) signaling in the context of AUD at the levels of the hypothalamic-pituitary-adrenal (HPA) axis and central amygdala (CeA). A functional increase in CeA GR activity occurs during alcohol withdrawal in alcohol-dependent animal models, and the GR antagonist mifepristone reduces alcohol-seeking and drinking behaviors in both rodents and humans. The aims of this study were to determine differential CeA protein expression in alcohol-dependent rats and examine the effects of mifepristone treatment in …

Total Synthesis Of The Marine Cytotoxic Mansouramycin And Derivatives, Aditya Dantu, Gabriella L. Madrigal, Neel Gondi, David Osazee, Ahmad Amro, Whard Alsabbagh, Shizue Mito

Research Colloquium

Purpose: Isoquinolinequinones are a group of organic compounds which are composed of an isoquinoline fused to a quinone ring. This class of molecules is known to exhibit a wide variety of biological activities, including cytotoxic and antitumor properties. Among the many families of isoquinolinequinones are the Caulibugulones and Mansouramycins, which exhibit anticancer properties and are thus desirable subjects for cancer-related research. They are obtained by isolation from marine bryozoan Caulibugula intermis and marine Streptomyces sp respectively, however these compounds are difficult to extract. Thus, organic synthesis is being explored as a method of obtaining them; this project focuses on the …

Advances In Indole Chemistry: Regiodivergent Annulations And Bridged Azacycle Synthesis, Zachary Tihomir Protich

Dartmouth College Ph.D Dissertations

An important aspect for the research and development of new drug therapies is the ability to use modular synthetic methods to rapidly access structurally diverse drug-like building blocks. Nitrogen-containing heterocycles represent one of the most prevalent structural motifs found in pharmaceutical agents and biologically active natural products. However, despite their ubiquity, existing methods for accessing these structures often remain limited in scope, efficiency, and structural diversity, particularly when targeting densely functionalized or sterically demanding scaffolds from simple starting materials.

To address this problem, the research described in this dissertation focuses on the design and development of (3+2) annulation reactions for …

Unplanned Hospitalization Among Advanced Prostate Cancer Patients By Diabetes Status: A Population-Based Study, Amy L. Shaver, Krupa Gandhi, Scott W. Keith, Nikita Nikita, Christopher C. Yang, Felix J. Kim, Hushan Yang, William K. Kelly, Stephen J. Freedland, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

BACKGROUND: Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.

METHODS: This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with …

Cholesterol Crystal Embolization Induced Kidney Disease, Shohan Pervaze, Shreya Mohandas, Pushkas Gopalan, Stephen A. Morse, Siddhartha Bajracharya, Landon A. Krone, Farshid Yazdi

School of Medicine Faculty Publications

Cholesterol crystal embolization (CCE) results from the release of cholesterol crystals from ruptured atherosclerotic plaques into circulation, resulting in the occlusion of small arteries and arterioles in various organs. Ischemia triggers a systemic inflammatory response resulting in vascular obstruction and organ dysfunction. Kidneys are often involved because of the proximity to the aorta and CCE in the kidneys can result in acute, sub-acute, or chronic kidney disease. There are many known risk factors for renal involvement of CCE, including iatrogenic and spontaneous causes. The pathophysiology of CCE includes complex pathways that lead to acute and chronic effects that can have …

Novel Piperidone And Bispidine Derivatives: A New Approach In Cancer Therapy, Lereen Khaled Youssry

Theses and Dissertations

Cancer remains the second leading cause of death worldwide. As a result, scientists have been trying to find novel therapeutic approaches that target specific metabolic pathways selective to tumor cells. In this study, two novel piperidone and bispidine derivatives, organic molecules that target polyamine metabolism, were synthesized, and their potential cytotoxic, antioxidant and anti-inflammatory effects were investigated. Polyamines are naturally occurring metabolites that were reported to be in excess at cancer cells and were accounted for tumor proliferation, invasion and metastasis. Accordingly, the novel piperidone and bispidine derivatives were expected to disrupt tumor growth and progression via up-regulation of key …

The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …

Synthesis Of Medicinally Privileged Spiro-Β-Lactams, Debasish Bandyopadhyay, Reinaldo Mendes, Subhash C. Chauhan

Research Symposium

Background: Four-membered cyclic amide, commonly known as β-lactam, has been playing a crucial role in drug discovery research since its discovery by Alexander Fleming in 1928 from Penicillium notatum. The β-lactam antibiotics are broadly effective against several bacterial infections through acylating the transpeptidase involved in cross-linking peptides to form peptidoglycan or periplasmic murein, which is a fundamental constituent of the bacterial cell wall for both the gram-positive (ten or more layers) and gram-negative (one or two layers) bacteria. Although for more than eight decades, β-lactams have been recognized as antibiotics, later, other medicinal activities of β-lactam derivatives have been …

Effect Of Steroids On The Progression Of Alzheimer's Dementia: A Retrospective Chart Review., Julijana Zoran Conic, Alexandra Chetty, Lily Chen, Audrey Marsh, Sean Barry, Rodney Pattabhi, Thomas Reske, Erwin Aguilar, Lobna Ali

School of Medicine Faculty Publications

Objectives: Alzheimer's disease (AD) is a prevalent age‐related neurodegenerative disease that affects millions of individuals in the United States. Neuroinflammation is a driver of the neurodegenerative changes that characterize AD, prompting interest in how inflammation can be modulated for treatment and prevention. Methods: ICD‐10 codes were quarried from electronic medical records to identify patients diagnosed with AD from 2012 to 2020. The patients were then divided into those who used systemic steroids and those who did not before the progression of their disease. Data on medication prescribed was used to measure the disease's progression. Clinical findings and laboratory results were …

Synthesis Of Small Molecules As Therapeutic Candidates, Savia Boyer

Electronic Theses & Dissertations (2024 - present)

RNA plays a critical role in many biological functions, such as normal cellular functions or disease-related processes. Regulating biological processes through RNA-based therapeutics can be employed by the reversible photoregulation of oligonucleotides. Azobenzene, a light-responsive compound that changes conformation when exposed to ultraviolet (UV) or visible light, is attached to cytidine phosphoramidite to be incorporated in a series of RNA oligonucleotides. The reversibility of the nucleoside and oligonucleotide is verified through UV melting point experiments. The modified oligonucleotide can change conformation upon light irradiation to stop reverse transcription (RT) in the presence of many different reverse transcriptase enzymes. This technique …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

Effects Of Modification In Limonene And Geraniol On The Properties Of Thermal Cured Polyurethane Films, Sauravkumar Rajeshbhai Patel

Electronic Theses & Dissertations

The increasing demand for green materials has inspired in-depth research into biobased polymers; among these polymers, polyurethanes stand out because of their widest range of applications: coatings, adhesives, and biomedical devices. The subject of this paper is the preparation of bio-based polyurethane films based on the polyols synthesized from renewable feedstocks such as limonene, geraniol, and soybean oil. Limonene and geraniol were chemically modified from natural sources such as citrus fruits and essential oils to high-functionality polyols. Characterization of such polyols showed that geraniol had the highest hydroxyl (OH) value and thus geraniol-based polyurethane films were highly influencing in reactivity …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Association Between Various Types Of Corticosteroids And Mortality For Severe Community-Acquired Pneumonia In Adults: A Systematic Review And Network Meta-Analysis, Peng Wang, Jun Wan, Qiaoyu You, Yuxin Zheng, Wenhao Xu, Jialing He, Liyuan Peng, Cuyubamba Dominguez Jorge Luis, Yuning Feng, Ping Xu, Xinrong Li, Weelic Chong, Yang Hai, Lu Jia, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

OBJECTIVE: This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.

DATA SOURCES: This study conducted …