Resveratrol and quercetin are two naturally occurring tumor suppressant and anti-inflammatory molecules found in plants. Chalcone and flavanone are two anti-inflammatory molecules that are structurally analogous to resveratrol and quercetin respectively and have been shown to gain tumor suppressant capabilities when derivatized. Halogenated derivatives of these special compounds were synthesized to increase bioactivity through structural modifications, lending sixteen total derivatives synthesized. Starting from halogenated benzaldehydes and certain acetophenones, a crossed aldol reaction was performed to yield the chalcone derivatives. The flavanone derivatives were synthesized from the chalcone derivatives using an intramolecular aldol condensation to perform a ring closure. The final products were all structurally analyzed using ¹H and ¹³C NMR spectroscopy, IR spectroscopy, CombiFlash flash chromatography, and X-ray crystallography.

Using Molecular Operating Environment (MOE), the sixteen synthesized derivates were tested on several potential enzyme targets to predict their potential for action on these enzymes in vitro. Docking scores of each derivative were analyzed against the docking scores of chalcone and flavanone, as well as quercetin and resveratrol, since many of the enzyme targets are inhibited by these molecules. These derivatives were then tested in vitro for cytotoxicity against HeLa cells using an MTT cytotoxicity assay. The docking scores for each derivative on these enzymes were analyzed against the cytotoxicity data to predict the true mechanism of action of these derivatives. Once the most likely target enzymes were chosen, medicinal chemistry transformations in cleft were performed on the current derivatives available to identify potential new synthetic targets. Future synthetic work will focus on synthesizing these derivatives and analyzing their potential as future treatments for certain cancers.

Alex Blank

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