Simple Choline Esters as Potential Anti-Alzheimer Agents

Title: Simple Choline Esters as Potential Anti-Alzheimer Agents

Volume: 16 Issue: 6

Author(s): Stefano Alcaro, Rosaria Arcone, Giosue Costa, Daniela De Vita, Michelangelo Iannone, Francesco Ortuso, Antonio Procopio, Raffaele Pasceri, Domenicantonio Rotiroti and Luigi Scipione

Affiliation:

Keywords: Choline esters, Alzheimer's disease, molecular modelling, enzymatic inhibition, electrocortical activity

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.

Cite this article as:

Alcaro Stefano, Arcone Rosaria, Costa Giosue, De Vita Daniela, Iannone Michelangelo, Ortuso Francesco, Procopio Antonio, Pasceri Raffaele, Rotiroti Domenicantonio and Scipione Luigi, Simple Choline Esters as Potential Anti-Alzheimer Agents, Current Pharmaceutical Design 2010; 16 (6) . https://dx.doi.org/10.2174/138161210790883796