%0 Journal Article
%T Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors.
%A Hu Z
%A Zhou S
%A Li J
%A Li X
%A Zhou Y
%A Zhu Z
%A Xu J
%A Liu J
%J Future Med Chem
%V 15
%N 20
%D 2023 10 30
%M 37902028
%F 4.767
%R 10.4155/fmc-2023-0206
%X Aim: 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). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC50 = 0.054 ± 0.004 μM; MAO-B: IC50 = 3.25 ± 0.20 μM), moderate inhibitory effects on self-mediated amyloid-β (Aβ) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.