Several cholinesterase inhibitors are either being utilized for symptomatic treatment of Alzheimer's disease or are in advanced clinical trials. E2020, marketed as Aricept, is a member of a large family of N-benzylpiperidine-based acetylcholinesterase (AChE) inhibitors developed, synthesized and evaluated by the Eisai Company in Japan. Based on these observations we have tried to discover novel acetylcholinesterase inhibitor using target search option in zinc database. Structure of target molecule zinc_634140 was obtained and docked against acetylcholinesterase (pdb id- 1eve) enzyme using Autodock 4.2. The docking studies divulge that compound zinc_634140 interact with receptor through hydrogen bonding with polar, acidic amino acid residues and showed close proximity towards greasy surface of receptor. The docking analysis suggest that compound zinc_634140 and E2020 (Aricept) showed nearly identical binding with acetylcholinesterase receptor. Further docking of compound zinc_634140 involved four water molecule while docking results of E2020 (Aricept) displayed involvement of two water molecule. Further optimization of compound zinc_634140 suggests addition of piperidine ring for future structural optimization to enhance arene-arene and arene-cation interactions with acetylcholinesterase receptor.
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