title: An efficient ionic liquid mediated synthesis, cholinesterase inhibitory activity and molecular modeling study of novel piperidone embedded α,β-unsaturated ketones.
abstract: A series of hitherto unreported piperidone embedded α,β-unsaturated ketones were synthesized efficiently in ionic solvent and evaluated for cholinesterase inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Most of the synthesized compounds displayed good enzyme inhibition; therein compounds 7i and 7f displayed significant activity against AChE with IC50 values of 1.47 and 1.74 µM, respectively. Compound 6g showed the highest BChE inhibitory potency with IC50 value of 3.41 µM, being 5 times more potent than galanthamine. Molecular modeling simulation was performed using AChE and BChE receptors extracted from crystal structure of human AChE and human BChE to determine the amino acid residues involved in the binding interaction of synthesized compounds and their relevant receptors.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Kia
authors.forename: Hasnah
authors.initials: H
authors.lastname: Osman
authors.forename: Raju Suresh
authors.initials: RS
authors.lastname: Kumar
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
authors.forename: Alireza
authors.initials: A
authors.lastname: Basiri
authors.forename: Kooi Yeong
authors.initials: KY
authors.lastname: Khaw
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia. osman.hasnah2012@yahoo.com.
authors.forename: Mohd Mustaqim
authors.initials: MM
authors.lastname: Rosli
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D052578:Ionic Liquids / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D052578:Ionic Liquids; D007659:Ketones; D010881:Piperidones; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase