Pharmacophore-based discovery of a novel cytosolic phospholipase A2α inhibitor

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Noha, Stefan M.^1,2  Jazzar, Bianca³  Kuehnl, Susanne^2,4  Rollinger, Judith M.^2,4  Stuppner, Hermann^2,4  Schaible, Anja M.⁵  Werz, Oliver⁵  Wolber, Gerhard⁶  Schuster, Daniela^1,2 

[1] Univ Innsbruck, Inst Pharm Pharmaceut Chem, Comp Aided Mol Design CAMD Grp, AT-6020 Innsbruck, Austria

[2] Univ Innsbruck, CMBI, AT-6020 Innsbruck, Austria

[3] Univ Tubingen, Inst Pharmaceut, Dept Pharmaceut Analyt, DE-72076 Tubingen, Germany

[4] Univ Innsbruck, Inst Pharm Pharmacognosy, AT-6020 Innsbruck, Austria

[5] Univ Jena, Inst Pharm, Chair Pharmaceut Med Chem, DE-07743 Jena, Germany

[6] Inst Pharm Pharmaceut Chem, DE-14195 Berlin, Germany

关键词: Cytosolic phospholipase A(2)alpha cPLA(2)alpha;    Inflammation;    Pharmacophore modeling;    Virtual screening;   

DOI  :  10.1016/j.bmcl.2011.11.093

来源: Elsevier

【 摘 要 】

The release of arachidonic acid, a precursor in the production of prostaglandins and leukotrienes, is achieved by activity of the cytosolic phospholipase A(2)alpha (cPLA(2)alpha). 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)alpha inhibitor in cell-free and cell-based in vitro assays. (C) 2011 Elsevier Ltd. All rights reserved.

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