title: Simple choline esters as potential anti-Alzheimer agents.
abstract: In this manuscript we report an integrated study to develop simple choline esters as cholinergic agents potentially useful against the Alzheimer disease. In previously reported experiments we demonstrated the capability of the pivaloylcholine to exert cholinergic effects into the Central Nervous System, so we decided to explore small variants of choline esters. The knowledge of crystallographic models of the enzymes involved in the hydrolysis of the acetylcholine allowed to consider the steric compatibility of some choline derivatives within their catalytic sites. The purpose of the work was to find out analogues with increased selectivity toward the acetylcholinesterase versus the butyrrylcholinesterase. Theoretical models were compared to enzymatic tests carried out with both enzymes and two different methods. In this screening we have selected two candidates for the in vivo experiments with pre-treated rats. Their electroencephalographic profiles were recorded and averaged before and after the intraperitoneal treatment with two compounds in comparison to the pivaloyl lead ester. The results demonstrated that one of the esters can exert biological effects similar to the parent compound.
authors.affiliation: Dipartimento di Scienze Farmacobiologiche Università Magna Graecia di Catanzaro, Campus Universitario, Viale Europa, Catanzaro, Italy. alcaro@unicz.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Rosaria
authors.initials: R
authors.lastname: Arcone
authors.forename: Giosuè
authors.initials: G
authors.lastname: Costa
authors.forename: Daniela
authors.initials: D
authors.lastname: De Vita
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Iannone
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Antonio
authors.initials: A
authors.lastname: Procopio
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pasceri
authors.forename: Domenicantonio
authors.initials: D
authors.lastname: Rotiroti
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002794:Choline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004593:Electrophorus; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004952:Esters; D006736:Horses; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D004952:Esters; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002794:Choline