title: Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE) inhibitors and bivalent cholinesterase (ChE) inhibitors represent new treatments for AD.
  
  
  RESULTS
  A series of lycorine derivatives (1-10) were synthesized and evaluated for anti-cholinesterase activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O-(methylthio)methyllycorine (7) was a dual inhibitor of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) with IC50 values of 11.40 ± 0.66 μM and 4.17 ± 0.29 μM, respectively. The structure-activity relationships indicated that (i) the 1-O-(methylthio)methyl substituent in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii) the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE than hAChE; and (iii) the oxidation of lycorine at C-2 decreases the activity.
  
  
  CONCLUSIONS
  Acylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE. Hence, further study on the modification of lycorine for ChE inhibition is necessary.
authors.affiliation: Key Laboratory of Economic Plants and Biotechnology, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China. wangyuehu@mail.kib.ac.cn.
authors.forename: Yue-Hu
authors.initials: YH
authors.lastname: Wang
authors.forename: Qin-Li
authors.initials: QL
authors.lastname: Wan
authors.forename: Cheng-Ding
authors.initials: CD
authors.lastname: Gu
authors.forename: Huai-Rong
authors.initials: HR
authors.lastname: Luo
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Long