title: A Current Perspective on the Inhibition of Cholinesterase by Natural and Synthetic Inhibitors.
abstract: 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.
authors.affiliation: Clinical Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir. India.
authors.forename: Anzer A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Clinical Biochemistry, Faculty of Biological Sciences, University of Kashmir, Hazratbal, 190006, Srinagar, Jammu and Kashmir. India.
authors.forename: Tanveer A
authors.initials: TA
authors.lastname: Dar
authors.affiliation: Clinical Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir. India.
authors.forename: Parvaiz A
authors.initials: PA
authors.lastname: Dar
authors.affiliation: Clinical Biochemistry, University of Kashmir, Hazratbal, Srinagar, Jammu and Kashmir. India.
authors.forename: Showkat A
authors.initials: SA
authors.lastname: Ganie
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, P.O. box 80216, Jeddah 21589. Saudi Arabia.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans
chemical_list: D002800:Cholinesterase Inhibitors
keywords: Alzheimer's disease; acetylcholine; acetylcholinesterase; butyrylcholinesterase; in silico docking; phytochemicals