Heterocycle Linked Ferrocenyl-Rhodamine System for Amyloid Fibril Inhibition Study

Abstract

Numerous processes like nucleation, oligomer association or dissociation, fibril maturation, aggregation and the creation of β-sheet enriched fibrillar structures are known as amyloids. This can be caused by amyloidogenic proteins tendency to misfold from their natural shape.1,2 The development and accumulation of insoluble fibrillar forms in tissue and organs contribute to neuropathic diseases including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and non-neuropathic conditions like type 2 diabetes.1 A novel solid supported selective functionalization approach was used to design rhodamine based fluorescent active ferrocenyl conjugated heterocyclic compounds to examine their inhibitory potential against the fibrillation of hen egg white lysozyme (HEWL) protein in acidic pH. Molecular docking studies have demonstrated strong interactions between the receptor molecules and the protein residues in the amyloid prone region, indicating a specific inhibitory potential because of the molecules unusual rotational flexibility.2 ThT fluorescence assay has been performed to understand the amyloid inhibition activity during the aggregation and disaggregation processes. Furthermore, the fluorescent active compounds were used to explore the change in their emission behaviour during the aggregation and disaggregation processes to monitor the amyloid inhibition in absence of external dye.