Organic Chemicals Commons^™

Computational Drug Design: A Multitargeted Approach In Bladder Cancer, Travis C. Lantz, Joydeb Majumder, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, …

Magnetic Field-Induced Intramolecular Cyclization As A Trigger For Nanoparticle-Based Delivery Systems., Sara Katherine Biladeau

Electronic Theses and Dissertations

Magnetic nanoparticles (MNPs) are used in a variety of applications, including as agents for magnetic resonance imaging, generation of local hyperthermia, and as platforms for drug delivery. Iron-based MNPs are often coated with a shell, such as silica or gold, to increase biocompatibility for drug delivery applications. Many MNPs used for cancer therapy rely on either an internal trigger, such as a difference in pH, or an external trigger, such as light or an alternating magnetic field (AMF), to cause release of a payload, typically a chemotherapeutic drug. Internal triggers are appealing because drug release can be targeted to a …

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero

Seton Hall University Dissertations and Theses (ETDs)

Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.

The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and thus the patients have to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Recent Advances On Iron Oxide Magnetic Nanoparticles As Sorbents Of Organic Pollutants In Water And Wastewater Treatment, Angela M. Gutierrez, Thomas D. Dziubla, J. Zach Hilt

Superfund Research Center Faculty Publications

The constant growth in population worldwide over the past decades continues to put forward the need to provide access to safe, clean water to meet human needs. There is a need for cost-effective technologies for water and wastewater treatment that can meet the global demands and the rigorous water quality standards and at the same maximizing pollutant efficiency removal. Current remediation technologies have failed in keeping up with these factors without becoming cost-prohibitive. Most recently, nanotechnology has been sought as the best alternative to increase access to water supplies by remediating those already contaminated and offering ways to access unconventional …

Natural Compounds Targeting Major Cell Signaling Pathways: A Novel Paradigm For Osteosarcoma Therapy., Pablo Angulo, Gaurav Kaushik, Dharmalingam Subramaniam, Prasad Dandawate, Kathleen Neville, Katherine Chastain, Shrikant Anant

Manuscripts, Articles, Book Chapters and Other Papers

Osteosarcoma is the most common primary bone cancer affecting children and adolescents worldwide. Despite an incidence of three cases per million annually, it accounts for an inordinate amount of morbidity and mortality. While the use of chemotherapy (cisplatin, doxorubicin, and methotrexate) in the last century initially resulted in marginal improvement in survival over surgery alone, survival has not improved further in the past four decades. Patients with metastatic osteosarcoma have an especially poor prognosis, with only 30% overall survival. Hence, there is a substantial need for new therapies. The inability to control the metastatic progression of this localized cancer stems …

Substituent Strength Vs Reactivity: A Study Of 1,3,4-Oxadiazoles And Electron Donating Groups, Katlynn Merringer

Undergraduate Honors Thesis Projects

This investigation focused on determining if there was a relationship between electron donating group substituent strength and resulting percent yield values of the 1,3,4-oxadiazole product. The data obtained from this investigation aimed to help chemists better understand the reactivity of the 1,3,4-oxadiazole because of its importance in the realm of drug design and development. In order to accomplish this, electron donating groups with varying pKa values were placed on the 1,3,4-oxadiazole and the resulting percent yields were analyzed for possible trends. The substituents used represented both resonance donating and inductively donating groups and were placed in both ortho and para …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Synthesis Of Multifunctional Polyacrylates And A Binding Group To Hemoglobin For The Treatment Of Traumatic Brain Injuries, Marina Michaud

Honors College Theses

Hemoglobin based oxygen carriers (HBOCs) hold promise as an effective emergency treatment of severe traumatic brain injuries (TBI). In the latest generation of HBOCs, polynitroxyl-pegylated hemoglobin (PNPH), cell-free hemoglobin is modified with TEMPO and PEG which reduce the toxicities associated with earlier generations of HBOCs. In our efforts to optimize the economic and therapeutic impacts of PNPH’s we have synthesized polydimethylaminoethyl methacrylate (poly-DMAEMA) under controlled living conditions via reverse addition-fragmentation chain transfer (RAFT) polymerization. The poly-DMAEMA was then successfully functionalized via quaternization of its NMe₂ groups using chloroacetate derivatives of the TEMPO and PEG. This process was quantitative and …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds, Hasan Al-Shiyab, Caroline Aziz

Student Scholar Symposium Abstracts and Posters

Fennel (Foeniculum vulgare) is a biennial Egyptian medicinal plant with an aromatic odor that belongs to the family Apiaceae (Umbelliferae). Fennel seeds are commonly used in traditional medicine, as they are known to have anti-inflammatory, anti-fungal and anti-cancerous activities. The major constituents of the fennel plant are sugars, minerals, essential fatty acids, proteins and fibers. Although, there are numerous studies on the medicinal properties of essential oils of the fennel seeds, but there is limited data reported on the proteins and peptides. The aims of this project are to fully characterize the primary structure of proteins and to determine their …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

The Synthesis Of 1,3-Difluoro-2-Methyl-4-Phenylbenzene From A One-Pot Reaction Of Difluorocarbene And 1-Phenyl-2-Methylcyclobutene, Ruth Felicitas Menger

Senior Honors Projects, 2010-2019

Previous studies show that 1,2-disubstituted cyclobutenes can be used in reaction with difluorocarbene to produce 1,3-difluorobenzenes. A pathway to the synthesis of these types of compounds is of interest due to their presence in fluoroquinolone antibacterials, resins, and insecticides. The synthesis is unique because the fluorine atoms from the difluorocarbene are not adjacent to each other when the ring expands to a benzene ring. This study focuses on the reaction of difluorocarbene with 1-phenyl-2-methylcyclobutene, which was synthesized in one-pot in 4 steps starting from 1-phenyl-1-propyne and zirconocene dichloride.

Characterization And Target Identification Of Ak301: A Novel Mitotic Arrest Agent, Michael J. Bond, Avijeet S. Chopra, Marina Bleiler, Michelle Yeagley, Eric Scocchera

University Scholar Projects

The Giardina Laboratory has recently identified AK301 as a novel mitotic arrest agent. This work aimed to characterize the arrest state induced by AK301 (EC₅₀ ~ 150nM) and identify the cellar targets responsible for the arrest. It was found that AK301 arrest is readily reversible upon withdrawal of AK301. Cells that slip from mitosis after removal of AK301 are sensitized to apoptosis. This was found to be unique for AK301 when compared to other mitotic arrest agents like colchicine, vincristine, and BI2536. Arrested cells were found to have increased ATM activity as well as an upregulation of p53 and …

Renewable Resources: The New “Fossil Fuel”, Christopher Huynh, Crystal Vinuya, Gabriel Samaniego, Desiree Caceres, Yessica Moran

Scholarly and Creative Works Conference (2015 - 2021)

Creating ethanol from renewable resources that can be found around our school campus.

Nitrogen And Phosphorus Availability From Various Composted Wastes For Use In Irish Agriculture And Horticulture, Alan Lee

Doctoral

Current environmental EU legislation promotes recycling and recovery from organic waste products. Compost has been identified as an alternative to inorganic fertilisers and animal slurries as a nutrient source for crop plants. This study aimed to investigate nitrogen (N) and phosphorus (P) availability from various composted waste through detailed characterisations, complemented by short term lab incubations and long term plant growth experiments. Twenty-five composts were selected and classified by their groups. The composts were characterised by multiple different analytical techniques. Two incubation studies were conducted. One investigating N and P mineralisation potential of the composts and the second on the …