Reduced Flavones to Probe Biological Performance Diversity and the Synthesis of Autophagy Modulators

Small-molecule libraries with biological performance diversity will contain many bioactive molecules that have diverse targets. This is a desired characteristic for high-throughput screening because it will reduce the number of molecules that need to be screened while improving the likelihood of finding a hit for even challenging targets. It is still unclear which chemical features of molecules are most predictive of biological performance diversity. The first chapter of this work describes the synthesis of a library of reduced flavones with diverse chemical properties and the testing of these molecules in Cell Painting and cell viability assays in order to determine if any of these properties predict biological performance diversity. The second chapter of this work describes the discovery and synthesis of two autophagy modulators. Autophagy is a metabolic process which enables the cell to degrade selected proteins, organelles, and other cellular components, and it has been implicated in many diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases. An autophagy inhibitor was synthesized as a potential cancer therapeutic, and an autophagy modulator was synthesized that shows potential for use as a therapeutic for Niemann-Pick Type C disease. These molecules will be further optimized for future in vivo studies.