Design, synthesis, and bioevaluation of benzamides: novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Abeta aggregation, and beta-secretase.

Article Details

Citation

Peng DY, Sun Q, Zhu XL, Lin HY, Chen Q, Yu NX, Yang WC, Yang GF

Design, synthesis, and bioevaluation of benzamides: novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Abeta aggregation, and beta-secretase.

Bioorg Med Chem. 2012 Nov 15;20(22):6739-50. doi: 10.1016/j.bmc.2012.09.016. Epub 2012 Sep 17.

PubMed ID
23041347 [ View in PubMed
]
Abstract

Alzheimer's disease (AD) is a multifactorial syndrome with several target proteins contributing to its etiology. In this study, we conducted a structure-based design and successfully produced a series of new multi-site AChE inhibitors with a novel framework. Compound 2e, characterized by a central benzamide moiety linked to an isoquinoline at one side and acetophenone at the other, was the most potent candidate with K(i) of 6.47nM against human AChE. Particularly, it showed simultaneous inhibitory effects against BChE, Abeta aggregation, and beta-secretase. We therefore conclude that compound 2e is a very promising multi-function lead for the treatment of AD.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
GalantamineAcetylcholinesteraseKi (nM)61.96N/AN/ADetails
TacrineAcetylcholinesteraseKi (nM)32.12N/AN/ADetails