Organic Chemicals Commons^™

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 …

Usage And Behavioral Data Of Consumers Using Hair Dye Products Containing 2-Methoxymethyl-P-Phenylenediamine, Monika Kock, Carsten Goebel, Lidia Mihailescu, Maike Seib, Agnieszka Malesa, Anthony Gaspari, Brunhilde Blömeke

Department of Dermatology and Cutaneous Biology Faculty Papers

The potent sensitizer PPD is considered a key sensitizer in hair dye contact allergy. Modification of its molecular structure to 2-methoxymethyl-p-phenylenediamine (ME-PPD) reduces its skin sensitizing potency. We investigated the usage, behavior, and tolerance profile of ME-PPD-containing professional hair color products in a specifically tailored proactive market surveillance program in hairdresser salons across 5 countries. Hairdressers completed record cards for their clients, which were evaluated at the end of the program. 497 individuals received in total 2461 hair color treatments with ME-PPD-containing hair color. Feedback on compatibility was provided for 194 individuals: 6 individuals reported intolerance reactions, which were assessed …

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 …

Synergistic Cefiderocol-Containing Antibiotic Combinations Active Against Highly Drug-Resistant Acinetobacter Baumannii Patient Isolates With Diverse Resistance Mechanisms, Justin Halim, Andrew P. Keane, Jeannete Bouzo, Tope Aderibigbe, Jessica A. Chicola, Katie T. Nolan, Keertana Jonnalagadda, Jason X. Tran, Valerie J. Carabetta

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Acinetobacter baumannii is a nosocomial pathogen known for rapidly developing resistance to nearly all antibiotics, including last-line agents. Cefiderocol, a novel siderophore cephalosporin, has shown in vitro activity against A. baumannii and is now used clinically, but resistance is emerging. Data on cefiderocol-based antibiotic combinations are limited.

OBJECTIVES: To evaluate the in vitro activity of cefiderocol alone and in combination with other antibiotics against XDR and PDR A. baumannii clinical isolates, and to explore resistance mechanisms underlying cefiderocol synergy.

METHODS: We tested 21 XDR/PDR clinical isolates and one NDM-1-producing strain using broth microdilution and checkerboard assays with cefiderocol and …

Choline-An Essential Nutrient With Health Benefits And A Signaling Molecule, Brianne C. Burns, Jitendra D. Belani, Hailey N. Wittorf, Eugen Brailoiu, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Choline has been recognized as an essential nutrient involved in various physiological functions critical to human health. Adequate daily intake of choline has been established by the US National Academy of Medicine in 1998, considering choline requirements for different ages, sex differences and physiological states (e.g., pregnancy). By serving as a precursor for acetylcholine and phospholipids, choline is important for cholinergic transmission and the structural integrity of cell membranes. In addition, choline is involved in lipid and cholesterol transport and serves as a methyl donor after oxidation to betaine. Extracellular choline is transported across the cell membrane via various transport …

The Effect Of Tranexamic Acid On Blood Coagulation In Primary Total Hip Arthroplasty Using Rotational Thromboelastometry: A Randomized Controlled Trial, Uzung Yoon, David Beausang, Elia Elia, Marc Torjman, Jeffrey Mojica, James J. Purtill, David Nazarian, P. Maxwell Courtney, Yoogoo Kang

Department of Anesthesiology Faculty Papers

BACKGROUND: Tranexamic acid (TXA), is commonly administered prophylactically to reduce blood loss in patients undergoing total hip arthroplasty (THA). However, its effect has never been studied. We hypothesized that no difference exists in the degree of fibrinolysis and blood loss between patients receiving prophylactic TXA and placebo.

METHODS: This double-blinded randomized-controlled trial included 50 patients undergoing primary THA in 2021-2023. Clinicaltrials.gov (NCT03897621). Rotational-thromboelastometry (ROTEM) were performed to test blood coagulability using non citrated whole blood (NATEM) and blood treated with TXA (T-APTEM). The intervention group received TXA intravenously. The placebo group received 0.9% sodium chloride solution. The primary outcome measure …

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 …

Chronic Inflammatory Pain And Chronic Thc Vapor Inhalation Alter Midbrain Neuronal Activity, Leslie K. Kelley, Nicholas W. Gilpin, Jason W. Middleton

School of Medicine Faculty Publications

In an effort to reduce reliance on opioids for the treatment of pain in the clinic, ongoing work is testing the utility of cannabinoid drugs as a potential alternative for treatment of chronic pain. We tested chronic delta-9 tetrahydrocannabinol (THC) vapor inhalation effects on intrinsic and synaptic properties of ventrolateral periaqueductal gray (vlPAG) neurons in male and female rats treated with complete Freund's adjuvant (CFA). We report that chronic THC vapor inhalation modulates intrinsic and synaptic properties of vlPAG neurons, including reductions in action potential firing rate and spontaneous inhibitory synaptic transmission in males, and that these effects occur specifically …

Menthalactone From Mentha Piperita L., A Monocot-Selective Bioherbicide, Adam Soltani

Honors Theses

The challenge of managing invasive weed species continues to affect the agricultural industry, presenting ecological, economic, and agronomic hurdles that lead to over 100 billion USD in annual crop losses globally. One such concern is the management of Agrostis stolonifera L., commonly known as creeping bentgrass, particularly due to its ability to form hybrids. This scenario underscores the urgent need for innovative, effective, and environmentally sustainable herbicides, steering the focus toward natural substances as potential candidates. We report here a promising natural lactone, commonly known as menthalactone, which is derived from Mentha piperita L. Its phytotoxic activity was assessed against …

Computationally Assessing The Specificity Of Receptor Tyrosine Kinase Inhibitors, Htoo Say

Theses/Capstones/Creative Projects

Receptor tyrosine kinases (RTKs) are vital to cell signaling processes such as growth, survival, and differentiation. Dysregulation through mutation or overexpression often contributes to cancer, making RTKs key therapeutic targets for tyrosine kinase inhibitors (TKIs). However, the low specificity of many TKIs leads to off-target effects. This project uses molecular docking to evaluate the binding affinities and selectivity of FDA-approved TKIs across 18 RTK subtypes. The dockings conducted revealed significant variability in binding affinities, with Sorafenib exhibiting strong specificity for EphB2 (-7.6 kcal/mol) and poor compatibility with EphA7 and ErbB4 (-3.0 kcal/mol). These findings underscore the role of specific molecular …

Effects Of Novel Dopamine D4 Receptor-Targeted Compounds On Locomotor Activity And Anxiety-Like Behavior In Male And Female Sprague Dawley Rats, Samantha Alyse Walkow, Noah A. Ivak, Daniel Chandler, John Tkaczynski, Thomas M. Keck, Comfort A. Boateng, Eleni Papadopoulos, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

The consequences of modulating subtypes of G protein coupled dopamine receptors are broadly studied for their role in decision making behavior, specifically in situations involving uncertain risk and reward. The actions of dopamine D4 receptors (D4Rs) on these complex processes are the least understood, particularly due to a lack of available compounds with suitable selectivity for D4Rs. Further, current research often fails to evaluate how modulating specific dopamine receptor subtypes may affect locomotor activity and anxiety-like behavior as confounding factors prior to assessing their function in behavioral assays of higher order decision making. The goal of the current study was …

Kratom As A Therapeutic Option For Opioid Use Disorder​: A Comprehensive Review​, Harmann Singh, Abdullah Noory, Akash M. Patel, Kush C. Patel, Simran Gandhi

Rowan-Virtua Research Day

Kratom (Mitragyna speciosa) has gained significant attention for its potential role in managing opioid use disorder (OUD). This review examines kratom’s pharmacology, safety profile, addiction potential, and ethical considerations in research, while exploring its future as a therapeutic option. Kratom’s primary alkaloids, mitragynine and 7-hydroxymitragynine, act as partial mu-opioid receptor agonists, producing analgesic and sedative effects at higher doses and stimulant-like effects at lower doses. Preclinical and observational studies suggest kratom may alleviate opioid withdrawal symptoms and cravings, but concerns remain regarding its dependency potential and adverse effects, including gastrointestinal distress, hepatotoxicity, and withdrawal symptoms upon cessation. While kratom carries …

Symptomatic Treatment Of Cannabis Withdrawal Syndrome: A Review Of The Existing Literature, Aria Sen, Dale Shober

Rowan-Virtua Research Day

Despite its public reputation as a recreational substance that does not cause physical withdrawal symptoms, cannabis withdrawal syndrome (CWS) was added to the DSM-5 in 2013. Existing research would suggest that almost half of regular cannabis users will experience symptoms such as mood symptoms, insomnia, and gastrointestinal distress. For more than 20 years, the rates of cannabis use have continued to trend upward due to expanding legislation on the recreational use of marijuana. Currently, there are no FDA approved treatments for CWS. Considering this trend, the lack of a well-formed treatment protocol for CWS will have a growing impact on …

The Anxiolytic Effects Of Ashwagandha Supplementation In Adults With Autism Spectrum Disorder And Anxiety, Jessica Mitchell, Andrea Iannuzzelli, Wendy Aita

Rowan-Virtua Research Day

BACKGROUND: The neuroendocrine system activates the hypothalamus-pituitary-adrenal (HPA) axis during stress,1 and individuals with autism spectrum disorder (ASD) may have atypical stress responses linked to HPA axis dysregulation.2 Prolonged activation of this system increases cortisol secretion, the body’s primary stress hormone.3 Withania somnifera (Ashwagandha) is a traditional herbal remedy believed to reduce stress by modulating the HPA axis and lowering cortisol levels.5

HYPOTHESIS: Following four weeks of Ashwagandha supplementation, the treatment group is expected to exhibit reduced cortisol levels, improved Aberrant Behavior Checklist (ABC) scores, and decreased stress-related behaviors, reflecting its anxiolytic effects.

METHODS: Forty-two adult participants with ASD and …

Radiofrequency Ablation Versus Naproxen For The Management Of Ankylosing Spondylitis: A Comparative Analysis, Akash Manish Patel, Alec Birnbaum, Yashas Sattur

Rowan-Virtua Research Day

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammation primarily affecting the spinal vertebrae and sacroiliac joints, leading to pain, stiffness, and progressive loss of spinal mobility.

Management typically focuses on alleviating symptoms and controlling inflammation to improve patient quality of life. In this study, we compared the efficacy of two common treatment modalities: radiofrequency ablation (RFA) and naproxen. RFA is a minimally invasive procedure that targets specific nerve endings to interrupt pain signals, whereas naproxen is a non-steroidal anti-inflammatory drug (NSAID) used to reduce inflammation and provide symptomatic relief. Our systematic review involved a cohort of AS …

Effects Of The Non-Stimulant Norepinephrine Reuptake Inhibitor, Atomoxetine, On Cognitive Flexibility In Healthy Adult Long-Evans Rats, Noah A. Ivak, Samantha Walkow, Christopher Knapp, Eleni Papadopoulos, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua Research Day

Executive function is the control of multiple higher order cognitive processes that include attention, working memory, and cognitive flexibility. Cognitive flexibility is the ability to shift behavioral strategies

in response to changing environmental demands and task complexity. This cognitive modality is often impaired in many neuropsychiatric disorders like attention deficit hyperactivity disorder (ADHD). Deficits in cognitive flexibility are associated with dysregulation of the catecholamines, norepinephrine (NE) and dopamine (DA) within the prefrontal cortex (PFC). Atomoxetine (ATX), a non-stimulant NE reuptake inhibitor, elevates levels of NE and DA in the PFC by inhibiting the norepinephrine transporter (NET). ATX is used to …

Examining The Relationship Between Sleep Habits And Caffeine Consumption, Daniel Calaff, Rachel Pruchno

Rowan-Virtua Research Day

Sleep is essential for cognitive function, mood regulation, immune defense, and metabolic health. Despite widespread caffeine use, its impact on sleep remains debated. It was initially hypothesized that higher caffeine consumption would correlate with greater sleep disturbances. This study explored the relationship between caffeine consumption and sleep habits in a general adult population using a Qualtrics-based self-report survey. Participants (n=93) reported average hours slept per night, time to fall asleep, and number of nighttime awakenings. Caffeine consumption was calculated based on reported intake and categorized into four dosage groups. Sleep outcomes were statistically compared using ANOVA, t-tests, and Pearson correlation. …

A Systematic Review On Cinacalcet’S Effect In Reducing Pth Serum Levels In Peritoneal Dialysis Patients, Akhil Gumidyala, Youssef Daoud, Mark Hanna, Han Jie Liu, Rikita Doshi

Rowan-Virtua Research Day

Background: Patients with Chronic Kidney Disease (CKD) have low calcium levels. Low blood calcium triggers the parathyroid gland to constantly secrete parathyroid hormone (PTH) in an attempt to raise blood calcium levels back to normal. One way PTH tries to do this is by removing calcium from bone. Chronically high PTH levels leads to increased bone resorption and increases the risk for bone fractures and mortality risk. This phenomenon is called secondary hyperparathyroidism (SHPT). Calcimimetics, like cinacalcet (sensipar), act similarly to calcium by binding allosterically to Calcium-Sensing Receptors (CaSR) on the parathyroid gland, thereby reducing PTH levels. The effect of …

A Rare Case Of Diffuse Alveolar Hemorrhage In The Setting Of Iga Nephropathy, Vasculitis And Atypical Hemolytic Uremic Syndrome In A Previously Healthy Young Adult, Karl Schlicht, Nancy Kaura

Rowan-Virtua Research Day

IgA Nephropathy, also known as Berger disease, can precipitate acute renal failure in patients. IgA Nephropathy (IgAN) is deposition of protein from IgA into the renal tissue with subsequent renal dysfunction. IgA vasculitis (IgAV) is another condition where similarly the protein of IgA is deposited into the vessels. There are some cases of co-existing atypical hemolytic uremic syndrome (aHUS) with IgAN. However, rare combinations seen with all three IgAN, IgAV, and aHUS without any pre-existing conditions nor medical history. Patients that develop any one of these conditions are looking at life long changes with hemodialysis (HD) and organ transplants being …

Investigation Of The Effects Of The Peptidylarginine Deiminase Inhibitor Cl-Amidine On Apoptosis And Gene Expression In Ovarian Cancer, Victoria Walden

Longwood Senior Thesis Proposal

Peptidylarginine deiminases (PADs) are a family of enzymatic proteins responsible for the conversion of arginine and methylarginine residues to citrulline. This conversion is important for several key cellular processes including transcriptional gene regulation. Recently, a link has been established between overexpression of a particular PAD, PAD4, and the accelerated progression of both autoimmune diseases and cancers. Ovarian cancer exhibits heightened levels of PAD4 in affected cells. High levels of PAD4 are associated with the formation of neutrophil extracellular traps (NETs) that promote cancer metastasis, and downregulation of the p53 apoptotic pathway. Thus, it is important to explore inhibitors of PAD4. …