Alzheimer Disease: Wei DQ

Zheng H, Wei DQ, Zhang R, Wang C, Wei H, Chou KC. · College of Life Sciences and Technology, Shanghai Jiaotong University, Minhang District, Shanghai, China. · Med Chem. · Pubmed #17897076 No free full text.

Abstract: To find new drug candidates for treating Alzheimer's disease, we used the similarity search technique and GTS-21 as a template to search the Traditional Chinese Medicines Database. The high-score molecules thus obtained were compared with the template through the flexible alignment. Those molecules which had good alignment with GTS-21 were selected for conducting the docking studies aimed at the alpha7 nicotinic acetylcholine receptor. The CHARMM22 force field was taken to compute the partial charge and the TABU search was adopted to operate the docking process. The docking results thus obtained were used to compare with that of GTS-21. Those molecules which had better docking results than that of GTS-21 were singled out for further consideration. Finally, it was found through an in-depth structural analysis that Mol 7235 might be a promising candidate for further modification by experiments to make it become an effective drug for treating Alzheimer's disease.

Wei DQ, Sirois S, Du QS, Arias HR, Chou KC. · Tianjin Institute of Bioinformatics and Drug Discoveries, Tianjin Normal University, Tianjin 300074, China. · Biochem Biophys Res Commun. · Pubmed #16256952 No free full text.

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.