Structure-Based Scaffold Repurposing toward the Discovery of Novel Cholinesterase Inhibitors.

ABSTRACT: Cholinesterases (ChE) are well-known drug targets for the treatment of Alzheimer's disease (AD). In continuation of work to develop novel cholinesterase inhibitors, we utilized a structure-based scaffold repurposing approach and discovered six novel ChE inhibitors from our recently developed DNA gyrase inhibitor library. Among the identified hits, two compounds (denoted 3 and 18) were found to be the most potent inhibitor of acetylcholinesterase (AChE, IC₅₀ = 6.10 ± 1.01 μM) and butyrylcholinesterase (BuChE, IC₅₀ = 5.50 ± 0.007 μM), respectively. Compound 3 was responsible for the formation of H-bond and π-π stacking interactions within the active site of AChE. In contrast, compound 18 was well fitted in the choline-binding pocket and catal

SUBMITTER: Dighe SN 

PROVIDER: S-EPMC7726787 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature