Degree
Doctor of Philosophy (PhD)
Department
Chemistry
Document Type
Dissertation
Abstract
Being among the top ten causes of death, cancer has constantly been able to grab the attention of researchers all around the world. While several treatment methods prevail to cure cancer, the seriousness of this medical condition requires continuous work in the development of novel treatments as well as scientific advancements in order to achieve early detection of the disease. Luminescence imaging is an emerging field in both diagnosis of diseases, as well as a means to provide guidance in clinical surgeries. While there exist only a few contrasting agents approved by the Food and Drug Administration, the need for the development of more contrasting agents with better qualities still remains. Here I present the attempts to develop such visualizing agents in order to be useful in image-guided surgery, using fluorescence and chemiluminescence as the modes of photon generation. These luminophores are proposed to target a biomarker over-expressed in cancer; human NAD(P)H: quinone oxidoreductase-1 enzyme (NQO1). Incorporating a trimethyl-locked quinone propionic acid as the trigger group, the probes Q3NNBTCy and Q3NDODCM were designed and synthesized. Being tripartite probes, these enzyme-activatable fluorescent probes are composed of a linker (N-methyl-p-aminobenzoyl alcohol) and a luminogenic reporter of choice. The probe Q3NNBTCy contains a benzothiazole-based heptamethine as the fluorescent reporter and was found to emit in the near-infrared region. The probe Q3NNBTCy also showed fluorescence in organic solvents, however, displayed low emission in aqueous media. HT-29 cells with high NQO1 activity showed bright fluorescence compared to H596 cells with no NQO1 activity. The probe Q3NDODCM contains an adamantylidene-dioxetane moiety, which could be capable of producing enough thermal energy to function as a chemiluminescent probe. However, this probe was not activated by the enzyme, possibly because it could act as an inhibitor to the enzyme.
Date
11-3-2022
Recommended Citation
Kankanamge, Ovini Vionika Weeratung, "Design, Synthesis, and Characterization of NQO1-Activatable Luminescent Probes" (2022). LSU Doctoral Dissertations. 6012.
https://repository.lsu.edu/gradschool_dissertations/6012
Committee Chair
McCarley, Robin L.
DOI
10.31390/gradschool_dissertations.6012
Included in
Analytical Chemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons