title: The discovery of new acetylcholinesterase inhibitors derived from pharmacophore modeling, virtual screening, docking simulation and bioassays.
abstract: Hyperactivity of acetylcholinesterase (AChE) in the brain is the immediate cause of Alzheimer's disease (AD), which is one of the most prevalent fatal diseases afflicting numerous older people. In this research, an in silico study was carried out to find potential AChE inhibitors from a large chemical library. With clustering and lots of comprehensive analysis, some molecules were screened using in vitro bioassays. The IC50values against AChE ranged from 33.620 to 101.570 μM, while the inhibition ratios at 50 μM ranged from 11.37% to 77.35%. The binding mode between the inhibitor and the binding sites of AChE was studied. Four residues (Tyr133, Tyr124, Ser203 and Trp86) were suggested to be crucial because they can form hydrogen bonds with the ligand. Therefore, ZYQ1 and its derivatives might represent a promising starting point for the development of highly potent lead compounds for the treatment of AD.
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn and University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Yunqin
authors: Y
authors: Zhang
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn.
authors: Shuqun
authors: S
authors: Zhang
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn and University of the Chinese Academy of Sciences, Beijing 100049, China.
authors: Guowei
authors: G
authors: Xu
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn.
authors: Hui
authors: H
authors: Yan
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn.
authors: Yinglan
authors: Y
authors: Pu
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. zuozhili@mail.kib.ac.cn and Yunnan Key Laboratory of Natural Medicinal Chemistry, Yunnan, 650201, China.
authors: Zhili
authors: Z
authors: Zuo
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001681:Biological Assay; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D016000:Cluster Analysis; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D057188:Workflow
chemical_list: D002800:Cholinesterase Inhibitors; D008024:Ligands; D000110:Acetylcholinesterase