Date of Project

4-29-2021

Document Type

Honors Thesis

School Name

College of Arts and Sciences

Department

Biology

Major Advisor

Dr. Amanda Krzysiak

Abstract

Cellular drug target discovery is an important step in any drugs journey from bench to bedside. This is true for our lab's 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, 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 protease concentration. Experimentally, 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 4-TFM, we have narrowed in on a library of potential protein targets in the hope of ultimately establishing the cellular component(s) the small molecule is or are interacting with, creating its signature anti-cancer effects.

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