Development of potent reversible selective inhibitors of butyrylcholinesterase as fluorescent probes.

ABSTRACT: Brain butyrylcholinesterase (BChE) is an attractive target for drugs designed for the treatment of Alzheimer's disease (AD) in its advanced stages. It also potentially represents a biomarker for progression of this disease. Based on the crystal structure of previously described highly potent, reversible, and selective BChE inhibitors, we have developed the fluorescent probes that are selective towards human BChE. The most promising probes also maintain their inhibition of BChE in the low nanomolar range with high selectivity over acetylcholinesterase. Kinetic studies of probes reveal a reversible mixed inhibition mechanism, with binding of these fluorescent probes to both the free and acylated enzyme. Probes show environment-sensitive emission, and additionally, one of them also shows sign

SUBMITTER: Pajk S 

PROVIDER: S-EPMC6968640 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature