Title : Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring - Zhou_2020_Dose.Response_18_1559325820938526 |
Author(s) : Zhou Y , Hu Y , Lu X , Yang H , Li Q , Du C , Chen Y , Hong KH , Sun H |
Ref : Dose Response , 18 :1559325820938526 , 2020 |
Abstract :
Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC50 = 1.4 muM). The binding mode prediction and kinetic analysis were performed to obtain detailed information about compound 5. Besides, a preliminary structure-activity relationship investigation of compound 5 was carried out for further development of the series. The present results provided a valuable chemical template with a novel scaffold for the development of selective BChE inhibitors. |
PubMedSearch : Zhou_2020_Dose.Response_18_1559325820938526 |
PubMedID: 32636723 |
Zhou Y, Hu Y, Lu X, Yang H, Li Q, Du C, Chen Y, Hong KH, Sun H (2020)
Discovery of a Selective 6-Hydroxy-1, 4-Diazepan-2-one Containing Butyrylcholinesterase Inhibitor by Virtual Screening and MM-GBSA Rescoring
Dose Response
18 :1559325820938526
Zhou Y, Hu Y, Lu X, Yang H, Li Q, Du C, Chen Y, Hong KH, Sun H (2020)
Dose Response
18 :1559325820938526