| Abstract | Alzheimer's Disease (AD) has a complex pathology that involves many potential players including, reactive oxygen species (ROS), mis-regulated metal ions, protein aggregations, and cholinergic signaling defects. Thus, many potential therapeutics being investigated are designed to target more than just one of these pathological components. However, to date, there has yet to be any approved drugs that effectively and safely cure or prevent the onset of AD. Green and co-workers have taken this multi-target directed ligand approach by designing and synthesizing metal chelating molecules that contain antioxidant and radical scavenging moieties. The idea behind this approach is that we can target mis-regulated metal ions and decrease ROS while also potentially effecting other players of AD pathology. To test and compare the potential application of the newly synthesized L4 to previously synthesized L2, various spectroscopic assays were utilized. These assays specifically looked at the ability to inhibit amyloid aggregation (a hallmark observed in AD patients), inhibit ROS production via redox cycling, and scavenge radical species. Results from the aggregation inhibition study were unexpected due to ligand-metal complex solubility within the assay conditions. L4 did show it could effectively prevent ROS production, primarily thanks to its stable metal binding conformation. Lastly, results from one of the radical scavenging assays showed increased potential of L4 compared to L2 to act as a radical scavenger while the second assay did not give the same results as expected but this was hypothesized to be due to reaction parameters. Overall, these finding still support the potential of L4 to act as a therapeutic agent for AD, but other modifications or studies must be performed for further validation. |
