SYNTHESIS OF P-GLYCOPROTEIN INHIBITOR COMPOUNDS Advisor: Professor Alexander R. Lippert Doctor of Philosophy conferred: August 4th, 2021 Dissertation completed: August 4th, 2021 A problem with cancer treatment is that many cancers develop resistance to chemotherapeutic agents, causing them to fail to accumulate in resistant cancer cells long enough to have any effect. This is due to the overexpression of a plasma membrane protein called P-glycoprotein (P-gp). Generally, the role of P-gp is to protect the cells from any toxins or foreign substances by pumping these toxins (including chemotherapeutic drugs) out of the cell. I am collaborating with the Wise-Vogel laboratory at Southern Methodist University, who utilize a computer-generated model to predict the structures of P-gp inhibitors that inhibit the action of P-gp. These docking models find drug targets that slow the action of P-gp pumping, as well as help understand the underlying mechanism of how the protein effluxes toxins from the cell. My current research is focused on multiple drug analogues that are predicted to inhibit the P-gp protein based on their docking models. They are tested in cancer cell lines in combination with current chemotherapeutics to determine efficacy and strength of inhibition so that future chemotherapeutic drugs can work effectively in cells.
Dr. Alexander R. Lippert
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Aljowni, Maha, "Synthesis of P-Glycoprotein Inhibitor Compounds" (2021). Chemistry Theses and Dissertations. 24.