title: Design and synthesis of newer potential 4-(N-acetylamino)phenol derived piperazine derivatives as potential cognition enhancers.
abstract: A series of novel hybrids has been designed, synthesized and evaluated for cognition enhancing activities through the inhibition of acetylcholinesterase (AChE) and by passive avoidance mouse model. All the compounds showed excellent AChE inhibition activities and potentially reversed the scopolamine induced memory deficit. Enzyme kinetic and molecular docking studies have confirmed their dual binding affinity and mixed type inhibition. Among them, compounds 1b and 2d displayed excellent IC50 values of 1.66μM and 0.49μM and competitive inhibitor constant Ki 43.66μM and 4.10μM respectively. Ex vivo study confirmed their CNS penetration and brain AChE inhibition abilities. Furthermore, 1b and 2d showed significant antiamnesic activity at a dose of 1.0mg/kg as compared to the reference compounds piracetam and rivastigmine. The results indicate that these two compounds emerged to be developed as cognition enhancers worthy of future pursuit.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India. Electronic address: ppvohra28in@yahoo.co.in.
authors.forename: Poonam
authors.initials: P
authors.lastname: Piplani
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
authors.forename: Chhanda Charan
authors.initials: CC
authors.lastname: Danta
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000627:Aminophenols / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D015195:Drug Design; D005260:Female; D016166:Free Radical Scavengers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014101:Torpedo
chemical_list: D000627:Aminophenols; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D010879:Piperazines; C000593094:p-(acetylamino)phenol; D000077489:Piperazine; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase inhibitors; Antiradical activity; Cognition; Molecular docking; Passive avoidance stepdown; Piperazine derivatives