Synthesis of novel metal-based redox regulators for the treatment of periodontitis (360G-Wellcome-211938_Z_18_Z)

Periodontitis, inflammation of the gums and supporting structures of the teeth, is the most common chronic inflammatory disease of humans and has been linked to the development of diabetes and cardiovascular disease through co-morbid systemic inflammatory processes. The tissue damage surrounding the teeth is initiated by a microbial imbalance within the dental plaque biofilm, however is propagated by a dysfunctional host immune-inflammatory response to the bacterial biofilm. Peripheral blood neutrophils which dominate the immune response are both hyperactive and hyper-reactive with respect to Reactive Oxygen Species (ROS) release, with periodontal tissues showing extensive damage through oxidative stress due to this immune response. Metal-based compounds have been previously shown to modulate the level of ROS within cancer cells and are currently being developed and utilised as potent anticancer treatments. This project concerns the synthesis of novel metal-based compounds to reduce the level of oxidative stress within periodontal cells, treating and reducing the inflammation. This will be achieved through the synthesis of novel metal-based compounds as well as novel bidentate ligands incorporating elements of known anti-inflammatory treatments.