Cancer therapeutics have wide ranging side effects on healthy cells due to low specificity targeting, resulting in limited treatment compliance. LAT1, an overexpressed transporter in cancer cells, has been investigated and targeted for drug delivery. LAT1 uses the rocking bundle mechanism for transport, and has been utilized as a conduit for drugs that mimic its natural substrates. Quinone derivatives are common anticancer pharmacores due to their mechanistic action with cellular nucleophiles, participation in ROS, and noncovalent interactions with DNA base pairs and topoisomerase enzymes. With the prevalence of LAT1 in cancers, 1,4-naphthoquinone pharmacores are ideal candidates for anti-cancer therapeutics linked to large neutral amino acids to increase preferential discrimination towards cancer cells. In silico studies have allowed for predictive structure analysis in our design of naphthoquinone-tyrosine derivatives.
