Exploration
into the Cellular Target of 4-Trifluoromethoxy Chalcone via DARTS Method
Jordan Stacy, Trevor Stantliff / jstacy@bellarmine.edu / Faculty Advisor: Amanda Krzysiak
Cellular drug target discovery is an
important step in any drugs journey from bench to bedside. This is true for our
labs molecule of interest, the Chalcone. The Chalcone molecule and its
derivatives have been identified as small, plant-derived secondary metabolites
that, when interacting with human cancer cell lines, trigger apoptotic pathways
leading to varying levels of cell death. One derivative in particular,
4-Trifluoromethoxy Chalcone (4TFM), was identified through screenings as
inducing the highest death rate in A549 cancer cells, in conjunction with
having the lowest IC50, making it a good candidate to use in searching for the
currently unknown cellular target of the Chalcone. Using Drug Affinity Response
Target Stability (DARTS) Method, we have begun that process, leveraging the
fact that a protein's ligand is able to shield its target from proteolysis at a
specific concentration. Incubation with and without drug can produce conserved
bands observable via gel electrophoresis, providing potential targeted and
protected proteins that can be identified through Mass Spectrometry. For 4TMF,
we are currently narrowing in on a library of potential protein targets in the
hope to ultimately establish the cellular component the small molecule is
interacting with, creating its signature anti-cancer effects.
Accepted for presentation at the
American Society of Biochemistry and Molecular Biology Conference, April 2021.