Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors.

Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC = 0.054 ± 0.004 μM; MAO-B: IC = 3.25 ± 0.20 μM), moderate inhibitory effects on self-mediated amyloid-β (Aβ) aggregation and antioxidant activity. In addition, compound exhibited low neurotoxicity. More importantly, compound showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. All results suggest that compound may become a promising lead of anti-AD drug for further development.