Design, synthesis, biological evaluation, and molecular modeling of coumarin-piperazine derivatives as acetylcholinesterase inhibitors.
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.
['Modh|Rahul P|RP|', 'Kumar|Sivakumar Prasanth|SP|', 'Jasrai|Yogesh T|YT|', 'Chikhalia|Kishor H|KH|']
D000110:Acetylcholinesterase D000544:Alzheimer Disease D002800:Cholinesterase Inhibitors D003374:Coumarins D015195:Drug Design D058851:GPI-Linked Proteins D006801:Humans D057927:Hydrophobic and Hydrophilic Interactions D062105:Molecular Docking Simulation D010879:Piperazines D021281:Quantitative Structure-Activity Relationship
Alzheimer's disease hAChE Docking Coumarin Piperazine Field-based activity model