title: Theoretical studies of Alzheimer's disease drug candidate 3-[(2,4-dimethoxy)benzylidene]-anabaseine (GTS-21) and its derivatives.
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 alpha7 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 alpha7 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.
authors.affiliation: Tianjin Institute of Bioinformatics and Drug Discoveries, Tianjin Normal University, Tianjin 300074, China. lifescience@san.rr.com
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Wei
authors.forename: Suzane
authors.initials: S
authors.lastname: Sirois
authors.forename: Qi-Shi
authors.initials: QS
authors.lastname: Du
authors.forename: Hugo R
authors.initials: HR
authors.lastname: Arias
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D001597:Benzylidene Compounds / Q000032:analysis / Q000737:chemistry*; D001665:Binding Sites; D001923:Brain Chemistry; D003198:Computer Simulation; D019281:Dimerization; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011725:Pyridines / Q000032:analysis / Q000737:chemistry*; D011978:Receptors, Nicotinic / Q000032:analysis / Q000737:chemistry*; D020539:Sequence Analysis, Protein; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D001597:Benzylidene Compounds; C579167:Chrna7 protein, human; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088936:3-(2,4-dimethoxybenzylidene)anabaseine