The primary goal of this research is to develop novel drugs based on the hydroxycinammic polyphenol scaffold. There is tremendous potential in this area of drug development as many natural molecules in this class (e.g., caffeic acid) exhibit potent and favorable direct effects on cancer cell signaling in vitro. However, almost invariably, the natural products themselves are reported to have poor ADMET drug properties in vivo, particularly poor absorption and metabolic profiles. This is often due to sub-optimal structural characteristics. We seek to address these problems through the design and synthesis of novel molecules possessing more desirable pharmacokinetic properties than the natural compounds. A series of fourteen new compounds is proposed, incorporating several unique bioisosteric characteristics, aimed at improving problematic ADMET characteristics, while maintaining favorable anti-cancer signaling. Cell proliferation assays to evaluate the effects of the synthetic compounds on the UM-UC14 (malignant bladder), and PC3 (malignant prostate) cancer cells will be employed, along with transepithelial cell monolayer model assays to assess the bioavailability of the synthetic compounds in vitro. This proposed research plays an important part toward establishing a new core group of cancer researchers and facilities at LSUS. This proposal highlights contributions toward the medicinal chemistry component of that research. This is important in fostering collaboration with several major medical centers in Shreveport. Health care is an important part of our local economy, University Health, along with Willis- Knighton and the Feist-Weiller Cancer Centers are all placing a strong emphasis on translating therapies from the benchtop to the bedside. This project also supports another key component of LBRN�s mission by tackling an important interdisciplinary research problem in the prevention and treatment of cancer.