Discovery of Depsides and Depsidones from Lichen as Potent Inhibitors of Microsomal Prostaglandin E2 Synthase-1 Using Pharmacophore Models

Authors

  • Julia Bauer,

    1. Department of Pharmaceutical Analytics, Pharmaceutical Institute, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen (Germany)
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  • Dr. Birgit Waltenberger,

    1. Institute of Pharmacy / Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80–82, 6020 Innsbruck (Austria)
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  • Stefan M. Noha,

    1. Institute of Pharmacy / Pharmaceutical Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80–82, 6020 Innsbruck (Austria)
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  • Dr. Daniela Schuster,

    1. Institute of Pharmacy / Pharmaceutical Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80–82, 6020 Innsbruck (Austria)
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  • Prof. Dr. Judith M. Rollinger,

    1. Institute of Pharmacy / Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80–82, 6020 Innsbruck (Austria)
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  • Prof. Dr. Joel Boustie,

    1. Institute of Chemical Sciences of Rennes, UMR CNRS 6226, Team PNSCM, University of Rennes 1, 2 Av Pr Léon-Bernard, 35043 Rennes Cédex (France)
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  • Dr. Marylene Chollet,

    1. Institute of Chemical Sciences of Rennes, UMR CNRS 6226, Team PNSCM, University of Rennes 1, 2 Av Pr Léon-Bernard, 35043 Rennes Cédex (France)
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  • Prof. Dr. Hermann Stuppner,

    1. Institute of Pharmacy / Pharmacognosy, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80–82, 6020 Innsbruck (Austria)
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  • Prof. Dr. Oliver Werz

    Corresponding author
    1. Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Philosophenweg 14, 07743 Jena (Germany)
    • Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Philosophenweg 14, 07743 Jena (Germany)
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Abstract

original image

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 (IC50 = 0.4 and 0.43 μM, respectively), indicating that these natural products have potential as novel anti-inflammatory agents.

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