Molecular docking and molecular dynamics simulation approaches for identifying new lead compounds as potential AChE inhibitors |
| |
Authors: | Jiancheng Shi Wentong Tu Min Luo |
| |
Institution: | College of Chemistry and Material Sciences, Guangxi Teachers Education University, Nanning, P.R. China |
| |
Abstract: | To provide hints for the design of novel acetylcholinesterase (AChE) inhibitors with higher potency and specificity, the binding modes of the (RS, S)-17b and (RS, R)-17b enantiomers on AChE were chosen to investigate by molecular docking and molecular dynamics simulation. The results show that the binding modes of (RS, S)-17b and (RS, R)-17b are clearly different from each other. In particular, the (RS, S)-17b and (RS, R)-17b enantiomers tend to be planar and bend conformations to interact with AChE, respectively. Furthermore, based on the binding mode on AChE and structure modification of (RS, S)-17b, two novel inhibitors (1 and 2) with higher inhibitory activity were designed. Our design strategy suggests that the number of N and O atoms should be increased, the 5, 6-dimethoxy should be transformed into ring and the indanone moiety should be ring-opening, which would result in generating potent and selective AChE inhibitors. |
| |
Keywords: | Molecular docking molecular dynamics simulation acetylcholinesterase (AChE) inhibitor Alzheimer’s disease (AD) |
|
|