Discovering New Acetylcholinesterase Inhibitors by Mining the Buzhongyiqi Decoction Recipe Data.
Myasthenia gravis (MG) is a neuromuscular disease that is conventionally treated with acetylcholinesterase (AChE) inhibitors, which may not fully remove the symptom for many reasons. When AChE inhibitors do not work, Chinese patients turn to Chinese medicine, such as the Buzhongyiqi decoction (BD), to treat MG. By elucidating the relations between the herbs of the Buzhongyiqi decoction recipe and AChE inhibitors with structure-based and ligand-based drug design methods and chemoinformatics approaches, we have found the key active components of BD. Using these key active components as templates, we have discovered five new AChE inhibitors through virtual screening of a commercial compound library. The new AChE inhibitors have been confirmed with Ellman assays. This study demonstrates that lead identification can be inspired by elucidating Chinese medicine. Since BD is a mixture, further studies against other drug targets are needed.
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou 510006, China.
Lu
L
Cui
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University, School of Medicine , 280 South Chongqing Road, Shanghai 200025, China.
Yu
Y
Wang
School of Pharmaceutical Sciences, Sun Yat-Sen University , 132 East Circle Road at University City, Guangzhou 510006, China.
Zhihong
Z
Liu
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University, School of Medicine , 280 South Chongqing Road, Shanghai 200025, China.
Hongzhuan
H
Chen
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University, School of Medicine , 280 South Chongqing Road, Shanghai 200025, China.
Hao
H
Wang
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine , Guangzhou 510006, China.
Xinxin
X
Zhou
School of Pharmaceutical Sciences, Sun Yat-Sen University , 132 East Circle Road at University City, Guangzhou 510006, China.
Jun
J
Xu
D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D008024:Ligands; D000110:Acetylcholinesterase