Synthesis of Substituted Stilbene Probes Towards the Investigation of Antagonistic Effects Observed with 3,5-Substituted Paraben Derivatives
In practice, antagonistic xenoestrogen compounds have been used as drugs to treat cancer. Traditional strategies, include preparation of estrogen receptor antagonists exhibiting high affinity for the receptor while preventing rearrangement of the AF-2 binding domain. In a potentially new strategy, substituted parabens have proven to act as antagonists but do not bear the large sidechain associated with this common antagonist strategy. Weak phenolic interactions make determining such paraben binding confirmations and mode of action difficult. To investigate these activities associated with hindered phenolic compounds, substituted bisphenol probes have been synthesized via Wittig protocols to produce a series of stilbene derivatives. Herein we present the synthesis of such substituted stilbenes. A model system was used to test the synthesis of many different molecules, with success towards one of the probes. Further work will need to be completed to complete the synthesis of all the probes to allow for testing using TR-FRET and ELISA assays. Antagonism is expected to arise from similar disruption in the role of H12 in the AF-2 ligand binding domain albeit due to alternative binding interactions.
Adams, Bethany, "Synthesis of Substituted Stilbene Probes Towards the Investigation of Antagonistic Effects Observed with 3,5-Substituted Paraben Derivatives" (2020). Longwood Senior Theses. 24.
Faculty Advisor: Dr. Andrew Yeagley
Committee Members: Dr. Benjamin Topham (Longwood University), Dr. Jonathan White (Longwood University), and Dr. Jason Pajski (University of Mount Olive).