Identification of Compounds for Butyrylcholinesterase Inhibition.
Article Details
- CitationCopy to clipboard
Li S, Li AJ, Travers J, Xu T, Sakamuru S, Klumpp-Thomas C, Huang R, Xia M
Identification of Compounds for Butyrylcholinesterase Inhibition.
SLAS Discov. 2021 Dec;26(10):1355-1364. doi: 10.1177/24725552211030897. Epub 2021 Jul 16.
- PubMed ID
- 34269114 [ View in PubMed]
- Abstract
Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic function like acetylcholinesterase (AChE) through hydrolyzing acetylcholine (ACh). Selective BChE inhibition has been regarded as a viable therapeutic approach in Alzheimer's disease. As of now, a limited number of selective BChE inhibitors are available. To identify BChE inhibitors rapidly and efficiently, we have screened 8998 compounds from several annotated libraries against an enzyme-based BChE inhibition assay in a quantitative high-throughput screening (qHTS) format. From the primary screening, we identified a group of 125 compounds that were further confirmed to inhibit BChE activity, including previously reported BChE inhibitors (e.g., bambuterol and rivastigmine) and potential novel BChE inhibitors (e.g., pancuronium bromide and NNC 756), representing diverse structural classes. These BChE inhibitors were also tested for their selectivity by comparing their IC50 values in BChE and AChE inhibition assays. The binding modes of these compounds were further studied using molecular docking analyses to identify the differences between the interactions of these BChE inhibitors within the active sites of AChE and BChE. Our qHTS approach allowed us to establish a robust and reliable process to screen large compound collections for potential BChE inhibitors.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Bambuterol Cholinesterase Protein Humans UnknownInhibitorDetails Rivastigmine Cholinesterase Protein Humans YesInhibitorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Acetylcholine Acetylcholinesterase Protein Humans NoSubstrateDetails Acetylcholine Cholinesterase Protein Humans NoSubstrateDetails