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Planta Med 2016; 82(11/12): 1110-1116
DOI: 10.1055/s-0042-108739
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Khaled Alsabil
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Sorphon Suor-Cherer
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Andreas Koeberle
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, Germany
,
Guillaume Viault
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Alexis Lavaud
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Veronika Temml
3   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
,
Birgit Waltenberger
3   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
,
Daniela Schuster
3   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
,
Marc Litaudon
4   Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, Labex LERMIT, Gif sur Yvette, France
,
Stefan Lorkowski
5   Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany
6   Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
,
René de Vaumas
7   Extrasynthese SA, Z. I Lyon Nord, Impasse Jacquard – CS 30062 69727 Genay Cedex, France
,
Jean-Jacques Helesbeux
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
David Guilet
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Hermann Stuppner
3   Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria
,
Oliver Werz
2   Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, Germany
,
Denis Seraphin
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
,
Pascal Richomme
1   SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France
› Author Affiliations
Further Information

Publication History

received 28 February 2016
revised 25 April 2016

accepted 02 May 2016

Publication Date:
10 June 2016 (online)

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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.

Key words

mPGES-1 - anti-inflammatory - garcinoic acid - tocotrienol - semisynthesis

* Dedicated to Professor Dr. Dr. h. c. mult. Kurt Hostettmann, 2014 Egon-Stahl Medal in Gold.


 

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