5 research outputs found
Design, Synthesis, and Structure−Activity Relationship of N‑Arylnaphthylamine Derivatives as Amyloid Aggregation Inhibitors
Dyes like CR are able to inhibit the aggregation
of Aβ fibrils. Thus, a screening of a series of dyes including
ABBB (1) was performed. Its main component 2 tested in an
in vitro assay (i.e., ThT assay) showed good potency at
inhibiting fibrils association. Congeners 4−9 have been
designed and synthesized as inhibitors of Aβ aggregation. A
number of these newly synthesized compounds have been
found to be active in the ThT assay with IC50 of 1−57.4 μM.
The most potent compound of this series, 4k, showed
micromolar activity in this test. Another potent derivative 4q
(IC50 = 5.6 μM) rapidly crossed the blood−brain barrier, achieving whole brain concentrations higher than in plasma. So 4q
could be developed to find novel potent antiaggregating βA agents useful in Alzheimer disease as well as other neurological
diseases characterized by deposits of amyloid aggregates