The goal of this project is to develop novel anticancer therapeutics based on amino acid conjugates with 1,4-naphthoquinones. Specifically, this work seeks to take advantage of the high nutrient needs of cancer cells through the design of drugs that mimic the natural substrates of an amino acid transporter, L-type amino acid transporter 1 (LAT1). LAT1 functions as a mediator for the uptake of crucial amino acids, and its expression is usually up-regulated in cancer cells and with the disease progression. Naphthoquinones are reported to play a crucial role in chemical defenses in plants and in bio-oxidative processes; examples include lapachol, shikonin and juglone which have been utilized traditionally for their diverse pharmacological properties (antimicrobial, anti-parasitic, antimalarial, anti-inflammatory, antiseptic, and anticancer activities). This research has two main objectives, (1) designing and synthesizing amino acid-1,4-naphthoquinone conjugates and analogues of these derivatives, and (2) investigating the anticancer activities of the molecules through a structure-activity relationship study. During this study, tyrosine, a natural LAT1 substrate, is used for the amino acid backbone, and known and novel naphthoquinone-based molecules are synthesized. The synthetic strategy for making the compounds and data on structural characterizations are presented.
