title: Design, synthesis, biological evaluation, and molecular modeling of coumarin-piperazine derivatives as acetylcholinesterase inhibitors.
abstract: Acetylcholinesterase (AChE) is an important drug target for the treatment of Alzheimer's disease. A novel series of coumarin-piperazine derivatives were synthesized and their potency to inhibit human AChE enzyme (hAChE) was studied. All the final compounds were characterized by infrared, (1)H NMR, (13)C NMR, and elemental analysis. Docking experiments of the designed coumarin-piperazine derivatives were carried out in order to compare the theoretical and experimental binding affinities toward hAChE, to delineate the inhibitory mechanism. Subsequently, a structure-activity relationship (SAR) study using the molecular field method showed that the hydrophobic field and positive charge center conferred by the coumarin and piperazine moieties demonstrated an inhibitory mechanism. Among the compounds tested, 3f, 3j, and 3m were found to be the most potent inhibitors of hAChE.
authors.affiliation: Department of Chemistry, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, India.
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Modh
authors.forename: Sivakumar Prasanth
authors.initials: SP
authors.lastname: Kumar
authors.forename: Yogesh T
authors.initials: YT
authors.lastname: Jasrai
authors.forename: Kishor H
authors.initials: KH
authors.lastname: Chikhalia
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D003374:Coumarins; D058851:GPI-Linked Proteins; D010879:Piperazines; C548244:ACHE protein, human; D000110:Acetylcholinesterase
keywords: Alzheimer's disease; Coumarin; Docking; Field-based activity model; Piperazine; hAChE