7-MEOTA and 2-aminobenzothiazole heterodimers: structure-mechanism relationship of amyloid inhibitors based on rational design

The formation and accumulation of amyloid aggregates are the accompanying phenomena of amyloidoses, which are currently untreatable and include Alzheimer's and Parkinson's diseases, diabetes mellitus, non-neuropathic lysozyme systemic amyloidosis and others. One of the very promising therapeutic approaches seems to be inhibition of amyloid formation and/or clearance of amyloid aggregates. Small molecules have a great potential to interfere with amyloid fibrillation of poly/peptides, which can be improved by connection of cyclic structures into single multicyclic molecule and their dimerization. In our study, we focused on heterodimers consisting of 7-MEOTA and 2-aminobenzothiazole (BTZ) parent molecules connected by an aliphatic linker. Using in vitro and in silico methods, we investigated the ability of studied compounds to inhibit the amyloid aggregation of hen egg white lysozyme (HEWL). Heterodimerization led to significant improvement of inhibitory activity compared to parent molecules. Moreover, the ...