alpha-synuclein and 1-3-indandione

The development of imaging agents for in vivo detection of alpha-synuclein (α-syn) pathologies faces several challenges. A major gap in the field is the lack of diverse molecular scaffolds with high affinity and selectivity to α-syn fibrils for in vitro screening assays. Better in vitro scaffolds can instruct the discovery of better in vivo agents. We report the rational design, synthesis, and in vitro evaluation of a series of novel 1-indanone and 1,3-indandione derivatives from a Structure-Activity Relationship (SAR) study centered on some existing α-syn fibril binding ligands. Our results from fibril saturation binding experiments show that two of the lead candidates compounds 8 and 32 bind α-syn fibrils with binding constants (K

Topics: alpha-Synuclein; Alzheimer Disease; Dose-Response Relationship, Drug; Drug Design; Humans; Indans; Ligands; Molecular Structure; Neuroprotective Agents; Protein Aggregates; Protein Folding; Structure-Activity Relationship