title: Catechol alkenyls from Semecarpus anacardium: acetylcholinesterase inhibition and binding mode predictions.
abstract: BACKGROUND
  The fruits of Semecarpus anacardium L. f. (Anacardiaceae) are used in Ayurvedic medicine and also in Iranian Traditional Medicine for various indications, among those for retarding and treatment of dementia.
  
  
  OBJECTIVE
  The severity of Alzheimer's disease obviously correlates with a cholinergic deficit. In a screening for acetylcholinesterase (AChE) inhibitory activity, an extract from the fruit resin of Semecarpus anacardium was among the most active ones. Thus, the aim of this study was to isolate the active compounds and to investigate them in detail. Their binding mode to the active site of AChE was investigated by in silico docking experiments.
  
  
  METHODS
  From a dichloromethane extract in an activity-guided fractionation the active compounds were isolated under use of different chromatographic techniques. Their structures were unambiguously identified by one and two-dimensional (1)H and (13)C NMR spectroscopy and mass spectrometry and their cholinesterase inhibitory activities were determined by a microplate assay. In order to compare the 3D active sites of AChE from Torpedo californica (TcAChE) and from Electrophorus electricus (EeAChE), three files from the Protein Data Bank (PDB) were used and for docking experiments, GOLD 3.1 software was employed. The concentrations of active compounds in the extract and the fruits were determined by HPLC analysis.
  
  
  RESULTS
  The active compounds were determined as 1',2'-dihydroxy-3'-pentadec-8-enylbenzene (A) and 1',2'-dihydroxy-3'-pentadeca-8,11-dienylbenzene (B). Their IC(50) values in an in vitro assay on AChE inhibition were determined as 12 and 34 μg/mL, respectively, while they were not active in the inhibition of butyrylcholinesterase (BChE). In silico docking experiments showed a similar bioactivity for compounds A and B. The concentration of compounds A and B in the fruits was 1.85% and 1.88%, respectively.
  
  
  CONCLUSIONS
  In the search for the active principle of the fruit resin of Semecarpus anacardium, compounds A and B were identified as two selective inhibitors for AChE versus BChE.
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: H R
authors.initials: HR
authors.lastname: Adhami
authors.forename: T
authors.initials: T
authors.lastname: Linder
authors.forename: H
authors.initials: H
authors.lastname: Kaehlig
authors.forename: D
authors.initials: D
authors.lastname: Schuster
authors.forename: M
authors.initials: M
authors.lastname: Zehl
authors.forename: L
authors.initials: L
authors.lastname: Krenn
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry* / Q000302:isolation & purification; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification; D005638:Fruit / Q000737:chemistry*; D007492:Iran; D008515:Medicine, Ayurvedic; D008519:Medicine, Traditional; D008958:Models, Molecular; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D031023:Semecarpus / Q000737:chemistry*
chemical_list: D000475:Alkenes; D002800:Cholinesterase Inhibitors; D010936:Plant Extracts; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase