A Comparative Evaluation of Acetylcholinesterase Inhibition by AChE-ICER and in vitro Ellman's Modified Method of Simplified Analogs 3-O-Acetyl-N-Benzyl-Piperidine of Donepezil

Author(s)

da Silva, Joyce Izidoro ; Nicastro, Patricia Carolina ; de Oliveira, Patricia C. M. ; Fossaluzza, Poliana C. ; Morais, Elida P. ; Dias, Kris Simone T. ; da Costa, Rodrigo S. ; Castro, Newton G. ; Cardoso, Carmen Lucia ; Viegas, Claudio, Jr.

• Document type: Journal article
• Source: REVISTA VIRTUAL DE QUIMICA; v. 7, n. 6, p. 13-pg., 2015-11-01.

Abstract

Acetylcholinesterase inhibitors (AChEI) remain the best pharmacotherapy for Alzheimer's disease (AD). Among the currently available AChEI drugs, Donepezil has longer half-life, fewer clinical side interactions, and satisfactory safety and tolerability; therefore, it is the first choice medicine to treat mild to moderate AD. Successful screening for new AChEIs relies on effective and fast assays. The most frequently employed assays are based on the use of Ellman's reagent (colorimetric method) or the Fast Blue B salt reagent, despite of other radiochemical, spectrometric, or chromatographic methods. A more recent and interesting approach is to immobilize the target enzyme in a chromatographic system, which is known as immobilized capillary enzyme reactors (ICERs). As part of a current project aiming to search for novel AChEIs, in this paper we have reported a comparative evaluation of AChE inhibitory activity of a series of substituted 3-O-acetyl-N-benzylpiperidine derivatives by two different approaches: in vitro Ellman's modified method and an ICER-based methodology. Although none of the compounds has shown high activity, all different assays revealed consistent results, showing that is possible to apply different reliable methodologies for the screening of new AChEIs. (AU)

• FAPESP's process: 08/04371-5 - Development and applications of enzymatic columns in selective inhibitors screening and in the natural products studies
• Grantee: Carmen Lúcia Cardoso
• Support Opportunities: Research Grants - Young Investigators Grants