Structure-based virtual screening leading to discovery of highly selective butyrylcholinesterase inhibitors with solanaceous alkaloid scaffolds.

ABSTRACT: According to recent research advance, it is interesting to identify new, potent and selective inhibitors of human butyrylcholinesterase (BChE) for therapeutic treatment of both the Alzheimer's disease (AD) and heroin abuse. In this study, we carried out a structure-based virtual screening followed by in vitro activity assays, with the goal to identify new inhibitors that are selective for BChE over acetylcholinesterase (AChE). As a result, a set of new, selective inhibitors of human BChE were identified from natural products with solanaceous alkaloid scaffolds. The most active one of the natural products (compound 1) identified has an IC₅₀ of 16.8 nM against BChE. It has been demonstrated that the desirable selectivity of these inhibitors for BChE over AChE is mainly controlled

SUBMITTER: Zhou S 

PROVIDER: S-EPMC6613991 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature