title: Discovery of depsides and depsidones from lichen as potent inhibitors of microsomal prostaglandin E2 synthase-1 using pharmacophore models.
abstract: Nature in silico: Virtual screening using validated pharmacophore models identified lichen depsides and depsidones as potential inhibitors of mPGES-1, an emerging target for NSAIDs. Evaluation of the virtual hits in a cell-free assay revealed physodic acid and perlatolic acid as potent inhibitors of mPGES-1 (IC(50) = 0.4 and 0.43 μM, respectively), indicating that these natural products have potential as novel anti-inflammatory agents.
authors.affiliation: Department of Pharmaceutical Analytics, Pharmaceutical Institute, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bauer
authors.forename: Birgit
authors.initials: B
authors.lastname: Waltenberger
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Noha
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Joel
authors.initials: J
authors.lastname: Boustie
authors.forename: Marylene
authors.initials: M
authors.lastname: Chollet
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D003198:Computer Simulation; D053630:Depsides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008011:Lichens / Q000737:chemistry*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008958:Models, Molecular; D000071876:Prostaglandin-E Synthases
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053630:Depsides; D007783:Lactones; C000875:depsidone; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases