LAUSR

The synthesis of new small chemical screening libraries (CSL) constructed from the intermediates of our total synthesis route of the uvaretin class of natural products is demonstrated herein. Numerous chalcone based CSLs were assembled, with varying substitution upon the phenolic groups within the chalcone core. Through cytotoxicity investigations it was found that the level of hydrophobicity of the phenolic core of the chalcones gives biases; less cytotoxicity with more hydrophobic cores. In addition to this, it was observed that potentiation property, evaluated with 6-thiopurine in the pancreatic cancer cell line MIA PaCa-2, is tunable with the inclusion of less hydrophobic character upon the phenolic core. The role of the o -hydroxybenzyl group, present within the uvaretin family, was revealed to be cytotoxic in character. Merging all of the structure-activity relationship studies performed, via the CSLs constructed in this effort, led to the construction of a new chalcone hybrid possessing both a cytotoxic enone group and a small molecule potentiating reduced enone group.