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

Abstract

A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced b-amyloid (Ab) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tryptamine or its derivative, connected through a a,w - alkyldiamide bridge. These hybrids exhibit moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity toward the AChE-induced Ab aggregation. Moreover, six out of the nine hybrids of this series exhibit a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.

Keywords

• Alzheimer’s disease
• acetylcholinesterase inhibitor
• Ab antiag-gregating activity
• oxoisoaporphine-tryptamine