Possible drug candidates for Alzheimer's disease deduced from studying their binding interactions with α7 nicotinic acetylcholine receptor

Ruo Xu Gu, Hui Gu, Zhi Yuan Xie, Jing Fang Wang, Hugo R. Arias, Dong Qing Wei, Kuo Chen Chou

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Dysfunction in α7 nicotinic acetylcholine receptor (nAChR), a member of the Cys-loop ligand-gated ion channel superfamily, is responsible for attentional and cognitive deficits in Alzheimer's disease (AD). To provide useful information for finding drug candidates for the treatment of AD, a study was carried out according to the following procedures. (1) DMXBA, a partial agonist of the α7 nAChR, was used as a template molecule. (2) To reduce the number of compounds to be considered, the similarity search and flexible alignment were conducted to exclude those molecules which did not match the template. (3) The molecules thus obtained were docked to α7 nAChR. (4) To gain more structural information, the molecular dynamics (MD) simulations were carried out for 9 most favorable agonists obtained by the aforementioned docking studies. (5) By analyzing the hydrogen bond interaction and hydrophobic/hydrophilic interaction, the following seven compounds were singled out as possible drug candidates for AD therapy: gx-50, gx-51, gx-52, gx-180, open3d-99008, open3d-51265, open3d-60247.

Original languageEnglish
Pages (from-to)250-262
Number of pages13
JournalMedicinal Chemistry
Volume5
Issue number3
DOIs
StatePublished - 18 Sep 2009
Externally publishedYes

Keywords

  • α7 nAChR
  • Chemical modification
  • DMXBA
  • Docking
  • MD simulation

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