title: Predicting cyclooxygenase inhibition by three-dimensional pharmacophoric profiling. Part II: Identification of enzyme inhibitors from Prasaplai, a Thai traditional medicine.
abstract: Prasaplai is a medicinal plant mixture that is used in Thailand to treat primary dysmenorrhea, which is characterized by painful uterine contractility caused by a significant increase of prostaglandin release. Cyclooxygenase (COX) represents a key enzyme in the formation of prostaglandins. Former studies revealed that extracts of Prasaplai inhibit COX-1 and COX-2. In this study, a comprehensive literature survey for known constituents of Prasaplai was performed. A multiconformational 3D database was created comprising 683 molecules. Virtual parallel screening using six validated pharmacophore models for COX inhibitors was performed resulting in a hit list of 166 compounds. 46 Prasaplai components with already determined COX activity were used for the external validation of this set of COX pharmacophore models. 57% of these components were classified correctly by the pharmacophore models. These findings confirm that the virtual approach provides a helpful tool (i) to unravel which molecular compounds might be responsible for the COX-inhibitory activity of Prasaplai and (ii) for the fast identification of novel COX inhibitors.
authors.affiliation: Institute of Pharmacy, Pharmacognosy, University of Innsbruck, 6020 Innsbruck, Austria.
authors.forename: Birgit
authors.initials: B
authors.lastname: Waltenberger
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Sompol
authors.initials: S
authors.lastname: Paramapojn
authors.forename: Wandee
authors.initials: W
authors.lastname: Gritsanapan
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
mesh_terms: D016861:Cyclooxygenase Inhibitors / Q000737:chemistry*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D008518:Medicine, East Asian Traditional; D008958:Models, Molecular; D008968:Molecular Conformation; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry*; D015203:Reproducibility of Results; D013785:Thailand
chemical_list: D016861:Cyclooxygenase Inhibitors; D010936:Plant Extracts