Synthesis and evaluation of catecholamine derivatives as amyloid-beta aggregation inhibitors

Abstract

Effectively inhibition of amyloid β (Aβ) aggregation is considered an important method for treatment of the Alzheimer's disease. Herein, inspired by the ability of trans-clovamide to effectively inhibit Aβ aggregation, we synthesized a series of structurally related catecholamine derivatives and tested them as Aβ aggregation inhibitors using the Thioflavin T assay. The results show that they demonstrated a higher inhibitory rate against Aβ aggregation. Furthermore, these compounds exhibited high water solubilities and low cytotoxicities. Additionally, transmission electron microscopy images and dynamic light scattering of their Aβ aggregations were observed. Docking simulations revealed that the catechol moiety of the synthesized compounds can form hydrogen bonds with the key regions of Aβ and thereby inhibit Aβ aggregation.

Keywords: Aggregation inhibition; Alzheimer’s disease; Amyloid β; Catechol derivatives.