title: Predicting Cyclooxygenase Inhibition by Three-Dimensional Pharmacophoric Profiling. Part I: Model Generation, Validation and Applicability in Ethnopharmacology.
abstract: 3D pharmacophore modeling has evolved as an established and state-of-the-art method for performing in-silico predictions of biological activity. Using one single model is limited to single binding modes, while the combination of several models bears a broader application scope. We demonstrate the generation of a complete and predictive 3D model set for cyclooxygenase 1 and 2 inhibitors, along with a selection and validation protocol optimized for parallel virtual screening. This model set was applied to explain the cyclooxygenase activity of an ethnopharmacologically known mixture of natural products, the Thai traditional medicine "Prasaplai". Results show that rationalizing natural product activity by modern in-silico approaches is promising and can be tremendously useful in the identification of the mechanisms of action for known biological effects of complex herbal remedies.
authors.affiliation: Computer-Aided Molecular Design Group, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria fax: (+43) 512-507-5269. Daniela.Schuster@uibk.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.affiliation: Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Waltenberger
authors.affiliation: Computer-Aided Molecular Design Group, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria fax: (+43) 512-507-5269.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.affiliation: Computer-Aided Molecular Design Group, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria fax: (+43) 512-507-5269.
authors.forename: Simona
authors.initials: S
authors.lastname: Distinto
authors.affiliation: Computer-Aided Molecular Design Group, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria fax: (+43) 512-507-5269.
authors.forename: Patrick
authors.initials: P
authors.lastname: Markt
authors.affiliation: Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria.
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.affiliation: Institute of Pharmacy/Pharmacognosy, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.affiliation: Computer-Aided Molecular Design Group, Department of Pharmaceutical Chemistry, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria fax: (+43) 512-507-5269.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
keywords: Cyclooxygenase inhibitors; Ethnopharmacology; Medicinal chemistry; Molecular modeling; Parallel screening; Prasaplai