Abstract
A series of unreported piperidone grafted spiropyrrolidines were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds, two compounds displayed higher AChE enzyme inhibitory activities than standard drug, galanthamine.
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•The new spiropyrrolidines showed good in vitro activity for AChE enzyme.•Two compounds displayed more potent AChE enzyme inhibition than standard drug galantamine.•Docking simulations of these two inhibitors showed good binding interactions to the active site channel of AChE enzyme.
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, which affected 35 million people in the world. The most practiced approach to improve the life expectancy of AD patients is to increase acetylcholine neurotransmitter level at cholinergic synapses by inhibition of cholinesterase enzymes. A series of unreported piperidone grafted spiropyrrolidines 8(a-p) were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Therein, compounds 8h and 8l displayed more potent AChE enzyme inhibition than standard drug with IC50 values of 1.88 and 1.37 µM, respectively. Molecular docking simulations for 8l possessing the most potent AChE inhibitory activities, disclosed its interesting binding templates to the active site channel of AChE enzymes. These compounds are remarkable AChE inhibitors and have potential as AD drugs.