Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: The discovery of potential acetylcholinesterase inhibitors: A combination of pharmacophore modeling, virtual screening, and molecular docking studies | Lu et al. Journal of Biomedical Science 2011 18 8 http content 18 1 8 BIN sc The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access The discovery of potential acetylcholinesterase inhibitors A combination of pharmacophore modeling virtual screening and molecular docking studies 11 11 3 3 Shin-Hua Lu Josephine W Wu Hsuan-Liang Liu Jian-Hua Zhao Kung-Tien Liu Chih-Kuang Chuang Hsin-Yi Lin1 Wei-Bor Tsai6 Yih Ho7 Abstract Background Alzheimer s disease AD is the most common cause of dementia characterized by progressive cognitive impairment in the elderly people. The most dramatic abnormalities are those of the cholinergic system. Acetylcholinesterase AChE plays a key role in the regulation of the cholinergic system and hence inhibition of AChE has emerged as one of the most promising strategies for the treatment of AD. Methods In this study we suggest a workflow for the identification and prioritization of potential compounds targeted against AChE. In order to elucidate the essential structural features for AChE three-dimensional pharmacophore models were constructed using Discovery Studio DS program based on a set of known AChE inhibitors. Results The best five-features pharmacophore model which includes one hydrogen bond donor and four hydrophobic features was generated from a training set of 62 compounds that yielded a correlation coefficient of R and a high prediction of fit values for a set of 26 test molecules with a correlation of R2 . Our pharmacophore model also has a high Guner-Henry score and enrichment factor. Virtual screening performed on the NCI database obtained new inhibitors which have the potential to inhibit AChE and to protect neurons from Ab toxicity. The hit compounds were subsequently subjected to molecular docking and evaluated by consensus scoring function which resulted in 9 compounds with .
