Term of Award
Fall 2025
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 and Biochemistry
Committee Chair
Karelle Aiken
Committee Member 1
Rebecca Kocerha
Committee Member 2
Abid Shaikh
Abstract
Globally, cancer is a leading cause of death. This has resulted in a great deal of attention dedicated to different types of therapeutic strategies to treat the disease. One strategy involves targeting the L-type amino acid transporter 1 (LAT1), a transmembrane transporter that enables cellular uptake of large neutral amino acids such as tyrosine. LAT1 is overexpressed in most types of cancers and plays a crucial role in supporting rapid proliferation, tumor growth, and metastasis. Naphthoquinones possess a range of therapeutic activities (antimalarial, antiparasitic, anticancer, and more) but can also be toxic toward healthy cells. Conjugating the naphthoquinone core with tyrosine has the potential to result in a therapeutic with enhanced selectivity for cancer cells over healthy cells. The assembly’s naphthoquinone unit would render the anticancer activity while its tyrosine moiety can enable selectivity via LAT1-recognizability. In this work, the design of the assembly takes advantage of the hydroxy group on the tyrosine side chain which is used as a linker unit. The synthetic approach involves a conjugate addition-elimination reaction under basic conditions. The primary objective of this research was to complete and optimize the synthetic steps for a series of tyrosine–naphthoquinone conjugates. This was accomplished, in part, by building upon previously established procedures. Modification of the methods for generating and isolating the compounds improved the overall yield and purity of the molecules of interest. The tyrosine conjugate frameworks included (1) a non-substituted, directly linked tyrosine-naphthoquinone conjugate, (2) two different sets of halogen-substituted derivatives and (3) triazole-containing analogs. For the latter two the incorporation of halogens and triazole are well known to increase the potency of small-molecule structures. Various characterization techniques were used to confirm the structures of the compounds.
Recommended Citation
Ashimi, Abdullahi A., "Developing Naphthoquinone-Tyrosine Conjugates As Targeted Cancer Therapeutics" (2025). College of Graduate Studies: Theses & Dissertations. 3053.
https://digitalcommons.georgiasouthern.edu/etd/3053
Research Data and Supplementary Material
No
