Pharmacophore-based drug design for potential AChE inhibitors from Traditional Chinese Medicine Database

Bioorg Chem. 2018 Feb:76:400-414. doi: 10.1016/j.bioorg.2017.12.015. Epub 2017 Dec 6.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder. Substrate-specific Acetylcholinesterase (AChE) plays a vital role in the AD treatment. Flavonoids with AChE inhibitory activities and low toxicity are used to developing new anti-AD agents. In this study, the best 3D QSAR pharmacophore model Hypo1 was generated by HypoGen program in Discovery Studio2016 based on the training set of flavonoids. We performed a virtual screening from Traditional Chinese Medicine (TCM), Druglike and MiniMaybridge databases using Hypo1. From docking analyses, we got the top 10 AChE inhibitors which were further evaluated by 8 different scoring functions. De Novo Evolution designed the top 10 derivatives, and three potential AChE inhibitor candidates were obtained eventually.

Keywords: AChE; AD; Docking; Flavonoids; Pharmacophore models; TCM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Algorithms
  • Binding Sites
  • Cholinesterase Inhibitors / chemistry*
  • Databases as Topic*
  • Drug Design*
  • Ligands
  • Medicine, Chinese Traditional*
  • Molecular Docking Simulation
  • Quantitative Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Ligands
  • Acetylcholinesterase