In Vitro Investigation Of Tumor Selective Piperidones As Therapeutic Agents Against Leukemia Cancer Cells

Cancer is a continuous global health issue. It is the second leading cause of death behind heart disease. Disparities across the emergence of cancer and resulting fatalities raise the importance of researching the disease. Treatments are available for certain types of cancers. However, these are typically accompanied by residual problems including side effects and the possibility for relapse. Some treatments attack all cells, leading to unwarranted side effects that make the possibility of living a comfortable life nearly impossible. Other treatments are specific to certain genetic alterations, making them only useful for a small percentage of patients. Not one treatment provides certainty of complete remission. Therefore, the need for novel treatments is still present and necessary. Research in the past decades has provided information on the mechanisms that cancer utilizes to persist. This has led to new approaches to attempt to target cancer cells. One approach is to manipulate the characteristics that cancer cells use to thrive within the body. An example of this is proteasome inhibition. Cancer cells rely on the proteasome to degrade proteins and transcription factors that could have negative effects on their persistence. Blocking cancer-supportive cellular machinery can lead to specific therapeutic effects on cancer cells. Drug discovery is a growing field. A critical aspect of anticancer drug discovery is to investigate the mechanism of action. This provides essential information on how the compound behaves within the cancer cells. Previous works have reported the cytotoxic effects of piperidone compounds, but the exact method has not been fully detailed. In this project, the investigation of the mechanism of action of potential anticancer piperidone drugs is described. Transcriptomic and computational analyses raise the impact of this research since these methods provide more concrete evidence. Detailed in this dissertation is the proteasome inhibition activity of four similarly structured piperidone compounds that could be used in future experiments to result in an improved anticancer therapy