Inhibition of fibril formation in beta-amyloid peptide by a novel series of benzofurans

dA series of benzofuran derivatives have been identified as inhibitors of f ibril formation in the beta-amyloid peptide. The activity of these compound s has been assessed by a novel fibril-formation-specific immunoassay and fo r their effects on the production of a biologically active fibril product. The inhibition afforded by the compounds seems to be associated with their binding to beta-amyloid, as identified by scintillation proximity binding a ssay. Binding assays and NMR studies also indicate that the inhibition is a ssociated with self-aggregation of the compounds. There is a close correlat ion between the activity of the benzofurans as inhibitors of fibril formati on and their ability to bind to beta-amyloid. Non-benzofuran inhibitors of the fibril formation process do not seem to bind to the same site on the be ta-amyloid molecule as the benzofurans. Thus a specific recognition site mi ght exist for benzofurans on beta-amyloid, binding to which seems to interf ere with the ability of the peptide to form fibrils.