Majority of the observed cognitive and behavioral changes in Alzheimer’s disease are postulated to be due
to the deficiencies in cholinergic pathways of the brain. Enhancement of cholinergic transmission may thus stimulate
the cholinergic receptors or prolong the availability of acetylcholine in synaptic cleft and hence improve the Alzheimer’s
disease associated symptoms. Of these two, the inhibition of cholinesterases (Acetylcholinesterase and Butyrylcholinesterase)
by cholinesterase inhibitors is suggested to be a promising strategy. In this regard, various agents
both natural and non-natural have been evaluated for the inhibition of cholinesterases. Phytochemical studies of some
of the medicinal plants have shown the presence of many valuable compounds that show a wide range of pharmacological
activity against cholinesterase enzymes. Interestingly, a good number of potent synthetic inhibitors of cholinesterase
enzymes reported so far are natural-product based. This article aims to provide a comprehensive overview of
both natural and synthetic cholinesterase inhibitors reported so far. Presenting a comparative overview of synthetic and
natural cholinesterase inhibitors may provide some leads for the synthesis of new cholinesterase inhibitors from medicinal
plants. Structural activity relationship of the active cholinesterase inhibitors is also discussed with some insights
from simulation studies. Insights for possible future research have also been highlighted.
Keywords: Alzheimer's disease, acetylcholine, acetylcholinesterase, butyrylcholinesterase, phytochemicals, in silico docking.
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