Design, synthesis and biological evaluation of bambuterol analogues as novel inhibitors of butyrylcholinesterase.

Jie Wu, Yiguang Tian, Shanping Wang, Marco Pistolozzi, Ya Jin, Ting Zhou, Gaurab Roy, Ling Xu, Wen Tan

European journal of medicinal chemistry 2017 Jan 27

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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. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Citation

Jie Wu, Yiguang Tian, Shanping Wang, Marco Pistolozzi, Ya Jin, Ting Zhou, Gaurab Roy, Ling Xu, Wen Tan. Design, synthesis and biological evaluation of bambuterol analogues as novel inhibitors of butyrylcholinesterase. European journal of medicinal chemistry. 2017 Jan 27;126:61-71