Amyloid Fibril Inhibition Study with Heterocycle Conjugated Ferrocenyl-Rhodamine Molecular System

Abstract

The tendency of amyloidogenic proteins to misfold from their native conformation can result in a number of processes, such as nucleation, fibril maturation, aggregation, oligomer association or dissociation and the formation of cross β-sheet enriched fibrillar structures known as amyloids.1,2 The growth and deposition of insoluble fibrillar structures in tissue and organs contribute to neuropathic illnesses 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 investigate their inhibitory ability against the fibrillation of hen egg white lysozyme (HEWL) protein in acidic pH. Strong interactions of the receptor molecule with the protein residues in the amyloid-prone region have been revealed from molecular docking study, depicting distinct inhibitory potential due to a unique rotational flexibility of the molecules.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.