title: Pharmacophore-based discovery of a novel cytosolic phospholipase A(2)α inhibitor.
abstract: The release of arachidonic acid, a precursor in the production of prostaglandins and leukotrienes, is achieved by activity of the cytosolic phospholipase A(2)α (cPLA(2)α). Signaling mediated by this class of bioactive lipids, which are collectively referred to as eicosanoids, has numerous effects in physiological and pathological processes. Herein, we report the development of a ligand-based pharmacophore model and pharmacophore-based virtual screening of the National Cancer Institute (NCI) database, leading to the identification of 4-(hexadecyloxy)-3-(2-(hydroxyimino)-3-oxobutanamido)benzoic acid (NSC 119957) as cPLA(2)α inhibitor in cell-free and cell-based in vitro assays.
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry, Computer-Aided Molecular Design (CAMD) Group and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80/82, AT-6020 Innsbruck, Austria.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Noha
authors.forename: Bianca
authors.initials: B
authors.lastname: Jazzar
authors.forename: Susanne
authors.initials: S
authors.lastname: Kuehnl
authors.forename: Judith M
authors.initials: JM
authors.lastname: Rollinger
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Anja M
authors.initials: AM
authors.lastname: Schaible
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wolber
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
mesh_terms: D062365:Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C574451:4-(hexadecyloxy)-3-(2-(hydroxyimino)-3-oxobutanamido)benzoic acid; D062365:Aminobenzoates; D004791:Enzyme Inhibitors; D010091:Oximes; D011994:Recombinant Proteins; D054513:Group IV Phospholipases A2