Novel hybrids of oxoisoaporphine–tryptAMine as inhibitors of acetylcholinesterase-induced β-AMyloid aggregation with improved antioxidant properties

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 significantin vitro inhibitory activity towards AChE-induced 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.