Term of Award
Spring 2024
Degree Name
Master of Science, Applied Physical Science
Document Type and Release Option
Thesis (restricted to Georgia Southern)
Copyright Statement / License for Reuse
This work is licensed under a Creative Commons Attribution 4.0 License.
Department
Department of Chemistry
Committee Chair
Karelle Aiken
Committee Member 1
Jannet Kocerha
Committee Member 2
Mark Vincent dela Cerna
Abstract
This structure-activity relationship (SAR) study investigates a 1,4-naphthoquinone-tyrosine assembly designed as a potential anticancer therapeutic to exploit the overexpression of the L-type amino acid transporter 1 (LAT1) in cancer cells. The long-term goal of this work is to address issues that can and often arise in cancer treatment due to cellular defense mechanisms, poor selectivity for cancer cells over healthy cells, and challenges with drug uptake. This ongoing project has two main objectives: (1) design and synthesis of 1,4-naphthoquinone derivatives and (2) biochemical characterization of the synthesized compounds in cancer cell lines. Studies involved commercially available scaffolds and synthesized 1,4 naphthoquinone derivatives, some of which are new to the literature. The derivatives, including the tyrosine-naphthoquinone assembly, were made from 2-bromo-1,4-naphthoquinone with yields ranging from 25%-75%. The tyrosine backbone, a substrate for LAT1, was selected because previous reports indicate the ability to enhance uptake using drug-LAT1 substrate assemblies. SAR investigations probed the relationship between structure and cytotoxicity in A549 (lung cancer), a cell line in which LAT1 is highly expressed. MTS assays, compound light microscopy, and confocal microscopy were used to determine the cytotoxic and morphological effects of the compounds. Results, thus far, are promising as the naphthoquinone-tyrosine assembly exhibited cytotoxic activity with A549 cells.
Recommended Citation
Seymour, Austin, "Design and Synthesis of Small Molecules as Potential Anticancer Therapeudics" (2024). Electronic Theses and Dissertations. 2785.
https://digitalcommons.georgiasouthern.edu/etd/2785
Research Data and Supplementary Material
No
