Detection/quantification of amyloid aggregation in solution using the novel fluorescent benzofuranone-derivative compounds as amyloid fluorescent probes: synthesis and in vitro characterization

Abstract

Neurodegenerative diseases are characterized by the presence of amyloid deposition. Thioflavin T (ThT) has been one of the molecules of choice to attempt the detection of the amyloid deposits, but ThT is unable to cross blood–brain barrier, due to its low lipophilicity. Therefore, there is strong motivation to design and develop new compounds for in vitro fibril detection as well as for in vivo amyloid imaging. Additionally, the importance and critical role of oxidative stress in the onset/progression of some neurodegenerative disorders, and therefore, the efficacy of aurone compounds in inhibiting the resulting toxicity have been frequently reported. In this study, we report the synthesis of some benzofuranone compounds and examine their antioxidant inhibitory property. Furthermore, to establish the potential detection of synthesized compounds to amyloid aggregates, their in vitro binding to some non-disease related amyloidogenic proteins were characterized. Analyses of the in vitro binding studies showed that compounds 3 and 4 bind to the fibril structures successfully while compounds 1, 2 and 5 indicated a low affinity binding to amyloid. Additionally, compounds 3 and 4 exhibited very good antioxidant properties. Furthermore, these compounds have a great potential as fluorescent probes for detecting amyloid aggregation for further investigations.