title: Discovery of new acetylcholinesterase inhibitors with small core structures through shape-based virtual screening.
abstract: Targeting acetylcholinesterase (AChE) using small molecule inhibitors is considered to be the most successful therapeutic strategy in the treatment of Alzheimer's disease (AD). Herein we present a shape-based virtual screening to identify new cores for the designing of AChE inhibitors. Ten active hits are identified and the most active hit, 5169-0032 and T5369186, showed comparable AChE inhibitory activity to tacrine. Prediction of physicochemical properties and ADME/T risk indicates their potential in druggability and safety. The two compounds provide new core and can serve as a promising fragment to design potent AChE inhibitors.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210038, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China.
authors.forename: Zong-liang
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210038, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, China.
authors.forename: Ting-ming
authors.initials: TM
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xuxiao_li@126.com.
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sunhaopeng@cpu.edu.cn.
authors.forename: Hao-peng
authors.initials: HP
authors.lastname: Sun
mesh_terms: D000631:Aminopyridines / Q000737:chemistry*; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A; D006801:Humans; D008403:Mass Screening; D008958:Models, Molecular
chemical_list: D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D051544:Cytochrome P-450 CYP3A
keywords: AChEIs; Dual site inhibitor; Shape-based screening; Small molecule; Virtual screening