title: An expedient, ionic liquid mediated multi-component synthesis of novel piperidone grafted cholinesterase enzymes inhibitors and their molecular modeling study.
abstract: Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 μM, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 μM. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 μM. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Basiri
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
authors.forename: Hasnah
authors.initials: H
authors.lastname: Osman
authors.forename: Raju Suresh
authors.initials: RS
authors.lastname: Kumar
authors.forename: Yalda
authors.initials: Y
authors.lastname: Kia
authors.forename: Khalijah Binti
authors.initials: KB
authors.lastname: Awang
authors.forename: Mohamed Ashraf
authors.initials: MA
authors.lastname: Ali
mesh_terms: D000818:Animals; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D052578:Ionic Liquids / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014101:Torpedo
chemical_list: D002800:Cholinesterase Inhibitors; D052578:Ionic Liquids; D010881:Piperidones; D002802:Cholinesterases
keywords: AChE; BChE; Ionic liquid; Molecular modeling; Multi-component reaction