2. Academic Validation
  3. Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors

Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors

  • Planta Med. 2016 Jul;82(11-12):1110-6. doi: 10.1055/s-0042-108739.
Khaled Alsabil 1,  Sorphon Suor-Cherer 1,  Andreas Koeberle 2,  Guillaume Viault 1,  Alexis Lavaud 1,  Veronika Temml 3,  Birgit Waltenberger 3,  Daniela Schuster 3,  Marc Litaudon 4,  Stefan Lorkowski 5,  René de Vaumas 6,  Jean-Jacques Helesbeux 1,  David Guilet 1,  Hermann Stuppner 3,  Oliver Werz 2,  Denis Seraphin 1,  Pascal Richomme 1
Affiliations

Affiliations

  • 1 SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
  • 2 Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, Germany.
  • 3 Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
  • 4 Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, Labex LERMIT, Gif sur Yvette, France.
  • 5 Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
  • 6 Extrasynthese SA, Z. I Lyon Nord, Impasse Jacquard - CS 30062 69727 Genay Cedex, France.
PMID: 27286327 DOI: 10.1055/s-0042-108739
Abstract

Over the last twenty years, tocotrienol analogues raised great interest because of their higher level and larger domain of biological activities when compared with tocopherols. Amongst the most promising therapeutic application, anti-inflammatory potency has been evaluated through the inhibition of various mediators of inflammation. Here, we worked on the isolation of two natural isoforms of garcinoic acid (i.e., δ and γ) from two different sources, respectively, Garcinia kola seeds and Garcinia amplexicaulis bark. We also developed semisynthetic strategies to access the other two non-natural α- and β-garcinoic acid isoforms. In the next stage of our work, microsomal prostaglandin E2 synthase was defined as a target to evaluate the anti-inflammatory potential of the four garcinoic acid isomers. Both dimethylated isoforms, β- and γ-garcinoic acid, exhibited the lowest IC50, 2.8 µM and 2.0 µM, respectively. These results showed that the affinity of tocotrienol analogues to microsomal prostaglandin E2 synthase-1 most probably contributes to the anti-inflammatory potential of this class of derivatives.

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