title: Applications of integrated data mining methods to exploring natural product space for acetylcholinesterase inhibitors.
abstract: Nature, especially the plant kingdom, is a rich source for novel bioactive compounds that can be used as lead compounds for drug development. In order to exploit this resource, the two neural network-based virtual screening techniques novelty detection with self-organizing maps (SOMs) and counterpropagation neural network were evaluated as tools for efficient lead structure discovery. As application scenario, significant descriptors for acetylcholinesterase (AChE) inhibitors were determined and used for model building, theoretical model validation, and virtual screening. Top-ranked virtual hits from both approaches were docked into the AChE binding site to approve the initial hits. Finally, in vitro testing of selected compounds led to the identification of forsythoside A and (+)-sesamolin as novel AChE inhibitors.
authors.affiliation: Department of Pharmacognosy, Institute of Pharmacy, University of Innsbruck, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Lisa
authors.initials: L
authors.lastname: Kern
authors.forename: Dimitar P
authors.initials: DP
authors.lastname: Hristozov
authors.forename: Lothar
authors.initials: L
authors.lastname: Terfloth
authors.forename: Bruno
authors.initials: B
authors.lastname: Bienfait
authors.forename: Christian
authors.initials: C
authors.lastname: Laggner
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Ulrike
authors.initials: U
authors.lastname: Grienke
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Johann
authors.initials: J
authors.lastname: Gasteiger
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057225:Data Mining / Q000379:methods*; D055808:Drug Discovery; D008958:Models, Molecular
chemical_list: D001688:Biological Products; D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase