title: A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole-pyrrolizine-piperidine hybrids.
abstract: A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13μM, respectively.
authors.affiliation: School of Chemical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
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: Subbu
authors.initials: S
authors.lastname: Perumal
authors.forename: Ibrahim Abdul
authors.initials: IA
authors.lastname: Razak
mesh_terms: D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D000078183:Oxindoles; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D007211:Indoles; D000078183:Oxindoles; D010880:Piperidines; D011758:Pyrroles; D013141:Spiro Compounds; C022960:2-oxindole; C032727:piperidine; D002091:Butyrylcholinesterase; D002802:Cholinesterases