Medicinal Chemistry

Dimitra Hadjipavlou-Litina
Aristotle University of Thessaloniki
Thessaloniki
Greece

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Possible Drug Candidates for Alzheimers Disease Deduced from Studying their Binding Interactions with α7 Nicotinic Acetylcholine Receptor

Author(s): Ruo-Xu Gu, Hui Gu, Zhi-Yuan Xie, Jing-Fang Wang, Hugo R. Arias, Dong-Qing Wei, Kuo-Chen Chou.

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 Alzheimers 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.

Keywords: α7 nAChR, DMXBA, docking, MD simulation, chemical modification

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2009
Page: [250 - 262]
Pages: 13
DOI: 10.2174/157340609788185909
Price: $58