Medicinal and Pharmaceutical Chemistry Commons^™

Determining The Bioaccumulation Of Minor Cannabinoids In Zebrafish Larvae, Kamdyn A. Holt

Honors Theses

Due to the increasing prevalence of cannabis product availability and usage in the modern United States, particularly among pregnant individuals, evaluating the bioaccumulation of minor cannabinoids to further understand the adverse effects of cannabinoids during early development is critical. This study quantitated the uptake of eight minor cannabinoids ((∆8-tetrahydrocannabinol (∆8-THC), ∆9-THC, ∆10-THC, cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabivarin (THCV), and hexahydrocannabinol (HHC)) in zebrafish larvae following water-borne 2 µM exposures from 6 to 96 hours post fertilization (hpf). Larvae were homogenized at 96 hpf and analyzed using a gas chromatography- mass spectrometry (GC-MS) method developed in this study. Bioconcentration …

Synthesis Of Tert-Butyl Ester And Ethyl Ester Prodrugs Of L-Gamma-Methyleneglutamic Acid Amides For The Treatment Of Cancer, Tristan D. Tran

Honors Theses

Metabolic pathways differ in cancer cells compared to noncancerous cells. Glutaminolysis is the primary producer of biosynthetic precursors in cancer cells, which allows for the cells to proliferate. In previous publications, the Le lab has established efficient synthetic routes to L-γ-methyleneglutamic acid amides which have shown to be as efficacious as tamoxifen and olaparib in inhibiting the growth of various breast cancer cell lines. These compounds have shown to inhibit the growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cell lines after 24 or 72 h of exposure. Furthermore, these compounds were selective in inhibiting the growth of cancer …

Effects Of Cannabichromene On Pain And Neuroinflammation In Hiv-1 Tat Transgenic Mice, Sydney Wheeler

Honors Theses

HIV-1 TransActivator of Transcription (Tat) is a vital regulatory protein involved in HIV replication and implicated in development of HIV-associated pain and neurocognitive deficits. Tat is thought to contribute to these pathologies through proinflammatory pathways. Developing mechanisms to curb Tat-mediated inflammation is a key step in improving the quality of life of those living with HIV. Both recreational and medicinal cannabis use is prevalent among many people living with HIV; given this prevalence and the perceived anti-inflammatory benefits of cannabis use, it is important to investigate how chemical constituents of cannabis may impact HIV. In the present study, the effects …

Synthesis Of Fluorinated Ketones For Biological Evaluation At The Gaba-B Receptor, Katherine Kreusel

Honors Theses

The proper functioning of the CNS depends on the balance between excitatory and inhibitory neurotransmitters. While excitation is primarily regulated by glutamate, inhibition is regulated by γ-aminobutyric acid (GABA). When GABA binds to a GABA receptor, there is a block in nerve transmission which is important when studying pain and drug addiction. There are two types of GABA receptors that are used as drug targets: GABA-A and GABA-B. While GABA-A receptors are ionotropic and ligand-gated ion channels, GABA-B receptors are G-protein coupled receptors that are used by cells to convert extracellular signals into intracellular responses. Although many therapeutics modulate the …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

In-Vitro Assessment Of Cb1/Cb2 Receptor Binding And Function, Joey M. Davis

Honors Theses

Cannabinoid receptors CB1 and CB2 are G protein-coupled receptors that have a variety of physiological effects on the human body. Many natural product agonists and antagonists are presumed to interact with the cannabinoid receptors and are therefore heavily studied in drug discovery. Assays are used to study the binding of compounds to these receptors. However, a limited number of these assays are efficient in determining the functional activity of ligands associated with CB1 and CB2. Of those, many use radioactivity which is both expensive and potentially dangerous to the researcher. In this study, we first validated the assays already found …

Synthesis Of Aromatic Fluorinated Ketones For Evaluation At The Gaba Receptor, Madeline Griffin

Honors Theses

GABA is a neurotransmitter that inhibits the excitation of neurons. Targeting this specific receptor has the potential to inhibit the central nervous system and possibly treat addiction, anxiety, or mood disorders. Previous research has shown that fluorinated ketones can have valuable applications in the medicinal chemistry of addiction. Some fluorinated ketones have shown activity at the GABA receptor. The main goal of this project was to synthesize aromatic fluorinated ketones for biological evaluation at the GABA_B receptor. Another goal was to compare both the monofluorinated and difluorinated analogues synthesized in order to quantify differences in activity from fluorination state. …

Studies Of Salvinorin-Based Antagonists To Elucidate Pertinent Interactions For Kappa Opioid Receptor Antagonism, Madeline Keane

Honors Theses

Opioid abuse, leading to addiction and related deaths, has created a chronic epidemic in the United States for the past 30 years. This crisis has sprung from reliance on the prescription of opioid analgesics as the primary method for the management of pain in the 1990s. At that time, these drugs, specifically Purdue Pharma’s OxyContin, were marketed as non-addictive. Due to this systemic minimization of the addictive properties of opioid analgesics, as prescription rates increased, opioid-related mortality rates climbed. This epidemic continues to be pervasive, as opioid-related overdose resulted in 47,600 deaths in 2017. In addition to the opioid epidemic, …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

Syntheses And Antimicrobial Activities Of Some 4-Aza-Sitostane Derivatives, Hassan Y. Aboul-Enein

Electronic Theses and Dissertations

Research into the chemical and pharmacological properties of aza­steroids has become of interest because of their potential value as pharmacodynamic and chemotherapeutic agents. A nitrogen atom, for example, would be able to interact, unlike carbon, with a variety of sites in enzymes by means of ionic-ionic, ionic-dipole, dipole-dipole and hydrogen.bonds. Azasteroids having a nitrogen, atom might be adsorbed more strongly or in a different orientation to a given enzyme, and also may produce.a different biologic effect with a new spectrum of biological activities. The pharmacological.activities of a number of synthetic azasteroids, have been reported.

This investigation is concerned with the …