Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors.
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.
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Khaled
K
Alsabil
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Sorphon
S
Suor-Cherer
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, Germany.
Andreas
A
Koeberle
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Guillaume
G
Viault
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Alexis
A
Lavaud
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Veronika
V
Temml
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Birgit
B
Waltenberger
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Daniela
D
Schuster
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, Labex LERMIT, Gif sur Yvette, France.
Marc
M
Litaudon
Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena, Germany.
Stefan
S
Lorkowski
Extrasynthese SA, Z. I Lyon Nord, Impasse Jacquard - CS 30062 69727 Genay Cedex, France.
René
R
de Vaumas
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Jean-Jacques
JJ
Helesbeux
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
David
D
Guilet
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Hermann
H
Stuppner
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena, Germany.
Oliver
O
Werz
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Denis
D
Seraphin
SONAS, SFR4207 QUASAV, University of Angers, Beaucouzé, France.
Pascal
P
Richomme
D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D029760:Garcinia / Q000737:chemistry*; D006801:Humans; D007536:Isomerism; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification* / Q000494:pharmacology; D000071876:Prostaglandin-E Synthases / Q000037:antagonists & inhibitors*
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D010936:Plant Extracts; C473370:garcinoic acid; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases