title: Cholinesterase inhibitory activity versus aromatic core multiplicity: a facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines.
abstract: Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes.
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Basiri
authors.affiliation: School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia. Electronic address: vicky@usm.my.
authors.forename: Vikneswaran
authors.initials: V
authors.lastname: Murugaiyah
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors.forename: Hasnah
authors.initials: H
authors.lastname: Osman
authors.affiliation: Department of Chemistry, College of Sciences, King Saud University, PO Box 2455, Riyadh, Saudi Arabia. Electronic address: sraju@ksu.edu.sa.
authors.forename: Raju Suresh
authors.initials: RS
authors.lastname: Kumar
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Kia
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
authors.forename: Alysha
authors.initials: A
authors.lastname: Hooda
authors.affiliation: Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Parsons
mesh_terms: D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D055772:Green Chemistry Technology; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010881:Piperidones / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D010881:Piperidones; D011743:Pyrimidines; D002091:Butyrylcholinesterase; D002802:Cholinesterases
keywords: AChE and BChE inhibitory activity; Aromatic core multiplicity; Domino cascade synthesis; Ionic liquids; Molecular modeling; Thiazolopyrimidines