Novel hybrids of oxoisoaporphine-tryptamine as inhibitors of acetylcholinesterase-induced β-amyloid aggregation with improved antioxidant properties

Abstract

A series of dual binding site acetylcholinesterase (AChE) inhibitors was designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced β-amyloid (Aβ) aggregation. The new hybrids consisted of a unit of 1-azabenzanthrone and tryptamine or its derivative, connected through an α,ω-alka(e)nediamide bridge. These hybrids exhibited moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity towards AChEinduced Aβ aggregation. Moreover, six of the nine hybrids of this series exhibited a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.