Theoretical studies of Alzheimer's disease drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine (GTS-21) and its derivatives

Dong Qing Wei, Suzane Sirois, Qi Shi Du, Hugo R. Arias, Kuo Chen Chou

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Theoretical and molecular modeling studies have been conducted for understanding the details of how 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (GTS-21) and its metabolism derivatives bind with the receptor of α7 nicotinic acetylcholine dimer. Good accordance with experimental results has been achieved. It was found that the van der Waals repulsion makes the dominant contribution to the binding energy. GTS-21 and its metabolites are apparently too large for the binding sites of the α7 dimer. To improve the effectiveness of the drug, a possible approach is to reduce its volume while maintaining the presence of the active groups. Our studies, in combination with experimental studies, will lead to a promising basis for practical drug design against Alzheimer's disease.

Original languageEnglish
Pages (from-to)1059-1064
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume338
Issue number2
DOIs
StatePublished - 16 Dec 2005
Externally publishedYes

Fingerprint

Dimers
Alzheimer Disease
Theoretical Models
Derivatives
Molecular modeling
Drug Design
Nicotinic Receptors
Metabolites
Binding energy
Metabolism
Pharmaceutical Preparations
Acetylcholine
Binding Sites
anabaseine
3-(2,4-dimethoxybenzylidene)anabaseine

Keywords

  • α7 Nicotinic acetylcholine receptor
  • Alzheimer's Disease
  • Docking
  • GTS-21
  • Molecular modeling
  • Structural bioinformatics

Cite this

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Theoretical studies of Alzheimer's disease drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine (GTS-21) and its derivatives. / Wei, Dong Qing; Sirois, Suzane; Du, Qi Shi; Arias, Hugo R.; Chou, Kuo Chen.

In: Biochemical and Biophysical Research Communications, Vol. 338, No. 2, 16.12.2005, p. 1059-1064.

Research output: Contribution to journalArticle

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