| Abstract
| - For the targeting selection of acetylcholinesterase (AChE) inhibitors from natural sources wegenerated a structure-based pharmacophore model utilizing an in silico filtering experimentfor the discovery of promising candidates out of a 3D multiconformational database consistingof more than 110 000 natural products. In our study, scopoletin (1) and its glucoside scopolin(2) emerged as potential AChE inhibitors by the virtual screening procedure. They were isolatedby different chromatographic methods from the medicinal plant Scopolia carniolica Jaqc. andtested in an enzyme assay using Ellman's reagent. They showed moderate, but significant,dose-dependent and long-lasting inhibitory activities. In the in vivo experiments (icv applicationof 2 μmol) 1 and 2 increased the extracellular acetylcholine (ACh) concentration in rat brainto about 170% and 300% compared to basal release, respectively. At the same concentration,the positive control galanthamine increased the ACh concentration to about the same level as1. These are the first in vivo results indicating an effect of coumarins on brain ACh.
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