Medicinal and Pharmaceutical Chemistry Commons^™

Alpha-Synuclein Interaction With Gedunin, Tony Matundura Nyabayo

Graduate Theses/Dissertations

Parkinson’s disease (PD) and other Proteinopathies develop when α-synuclein misfolds and aggregates into toxic amyloids. While existing treatments for PD are primarily focused on managing its symptoms, a viable solution for slowing down the progress of Parkinson’s disease involves targeting the toxic α-synuclein amyloids. Gedunin, a natural inhibitor of heat shock protein 90, has been extensively used to treat malaria. Also, recent research investigations have shed light on its potential beyond malaria therapy, indicating that Gedunin may offer a possible solution for treating a variety of neurodegenerative diseases. Using plate-based assays, we examined how Gedunin influences α-synuclein fibrillation and its …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Synthesis Of Tu100 Analogs And Biological Assays, Feyisope Tonye Oladapo

College of Graduate Studies: Theses & Dissertations

TU100 (14-methyl-5H-5,12-epiminobenzo[4,5]cyclohepta[1,2-b]naphthalene-6,11,13(12H)-trione) exhibits exceptional chemotherapeutic properties. It operates via a distinct mechanism that triggers cell death to create cytotoxic effects while concurrently inhibiting topoisomerase I and II. Its efficacy rivals that of well-known chemotherapeutic drugs like Daunorubicin. The distinctive characteristics of TU100 have led to initiatives aimed at creating structurally similar compounds to discover even more effective bioactive alternatives.

The analog synthesis incorporated quinoxaline or its derivatives (diphenyl quinoxaline, dipyridinyl quinoxaline, and dibenzophenazine-10,13-dione) that have been shown to have promising chemotherapeutic effects. Synthesizing the hetero naphthoquinones required a multi-step synthetic process, so quinoxaline/ derivatives intermediates are first prepared, then the …

Rational Design Of Small Molecules Targeting Mitochondrial Redox Proteins, Matheus Barbosa Belchior

Graduate Theses, Dissertations, and Problem Reports (ETD)

Reactive oxygen species play a crucial role in many cellular processes. Despite being a natural byproduct of cellular metabolism, overexpression of these species causes damage to the cell, leading to cell dysfunction. Central to the regulation of these highly reactive molecule is the mitochondria. Impairment in its function has been associated with oxidative stress within the cell. Herein, a ligand-based and structure-based approach to design new small molecules to inhibit mitochondrial redox proteins associated with oxidative stress and reactive oxygen species. In the first project two molecules were synthesized and characterized as potential monoamine oxidase B inhibitors. Results showed two …

Development Of Novel Carbohydrate-Based Nanoparticles For Precision Drug Delivery, Krystal Ann Hughes

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticle-based drug delivery has made tremendous advancements in the last decade. However, several critical factors, including precision drug delivery at the site of interest, long-term storage stability, and controlling release profiles of drugs in the systemic circulation, need to be addressed for successful clinical translation of nanomedicine. This dissertation presents novel carbohydrate-based nanoparticles that achieve precise intracellular delivery and therapeutic release at the disease site. We present the formulation and optimization of polymeric and polymer-lipid hybrid nanoparticles that enable precision intracellular delivery and passive accumulation of therapeutics in the bone marrow. Intracellular delivery is highly impactful and sought after. One …