title: Design, synthesis and biological evaluation of bambuterol analogues as novel inhibitors of butyrylcholinesterase.
abstract: An increase activity of butyrylcholinesterase is believed to contribute to Alzheimer's disease. Bambuterol is a known potent inhibitor of butyrylcholinesterase, but it has undesired cardiac effects and less lipophilicity. Thirteen bambuterol analogues were synthesized using 1-(3, 5-dihydroxyphenyl) ethanone as a starting material. In-vitro cholinesterase assay established that the majority of the compounds are specific butyrylcholinesterase inhibitors. Out of the 13 compounds, two bambuterol derivatives, BD-6 and BD-11 exhibited similar efficacies in inhibiting butyrylcholinesterase with fewer effects on heart and enhanced possibilities of permeating through the blood-brain barrier as compared to bambuterol. These bambuterol analogues may provide better alternatives for treatments of Alzheimer's disease.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Tian
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Shanping
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Marco
authors.initials: M
authors.lastname: Pistolozzi
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Gaurab
authors.initials: G
authors.lastname: Roy
authors.affiliation: Keypharma Biomedical Inc., Songshan Lake Science and Technology Industry Park, Dongguan, Guangdong, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Pre-Incubator for Innovative Drug and Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China; Institute of Biomedical & Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, Guangdong, People's Republic of China. Electronic address: went@gdut.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000328:Adult; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D015195:Drug Design; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D013726:Terbutaline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D013726:Terbutaline; C047766:bambuterol
keywords: Alzheimer's disease; Bambuterol; Butyrylcholinesterase; Specific butyrylcholinesterase inhibitor; YWGBVRAEPOSYRZ-BNMXMQCQSA-N