Structure-activity relationship of acridine derivatives to amyloid aggregation of lysozyme

Abstract

BackgroundAmyloid-related diseases (such as Alzheimer's disease or diabetes type II) are associated with self-assembly of protein into amyloid aggregates. MethodsSpectroscopic and atomic force microscopy were used to determine the ability of acridines to affect amyloid aggregation of lysozyme. ResultsWe have studied the effect of acridine derivatives on the amyloid aggregation of lysozyme to investigate the acridine structure-activity relationship. The activity of the effective planar acridines was characterized by the half-maximum depolymerization concentration DC50 and half-maximal inhibition concentration IC50. For the most effective acridine derivatives we examined their interaction with DNA and their effect on cell viability in order to investigate their eventual influence on cells. We thus identified planar acridine derivatives with intensive anti-amyloid activity (IC50 and DC50 values in micromolar range), low cytotoxicity and weak ability to interfere with the processes in the cell. ConclusionsOur findings indicate that both the planarity and the tautomerism of the 9-aminoacridine core together with the reactive nucleophilic thiosemicarbazide substitution play an important role in the anti-amyloid activities of studied derivatives. General significanceThe present findings favor the application of the selected active planar acridines in the treatment of amyloid-related diseases.