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.

Simple Choline Esters as Potential Anti-Alzheimer Agents / Stefano, Alcaro; Rosaria, Arcone; Giosue, Costa; DE VITA, Daniela; Michelangelo, Iannone; Francesco, Ortuso; Antonio, Procopio; Raffaele, Pasceri; Domenicantonio, Rotiroti; Scipione, Luigi. - In: CURRENT PHARMACEUTICAL DESIGN. - ISSN 1381-6128. - STAMPA. - 16:6(2010), pp. 692-697. [10.2174/138161210790883796]

Simple Choline Esters as Potential Anti-Alzheimer Agents

DE VITA, DANIELA;SCIPIONE, Luigi
2010

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.
2010
alzheimer's disease; choline esters; electrocortical activity; enzymatic inhibition; molecular modelling
01 Pubblicazione su rivista::01a Articolo in rivista
Simple Choline Esters as Potential Anti-Alzheimer Agents / Stefano, Alcaro; Rosaria, Arcone; Giosue, Costa; DE VITA, Daniela; Michelangelo, Iannone; Francesco, Ortuso; Antonio, Procopio; Raffaele, Pasceri; Domenicantonio, Rotiroti; Scipione, Luigi. - In: CURRENT PHARMACEUTICAL DESIGN. - ISSN 1381-6128. - STAMPA. - 16:6(2010), pp. 692-697. [10.2174/138161210790883796]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/46403
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