Semisynthetic and Natural Garcinoic Acid Isoforms as New mPGES-1 Inhibitors
| Autor: | David Guilet, Birgit Waltenberger, Guillaume Viault, Andreas Koeberle, Jean-Jacques Helesbeux, Pascal Richomme, Veronika Temml, Alexis Lavaud, Oliver Werz, Denis Séraphin, Marc Litaudon, Sorphon Suor-Cherer, Hermann Stuppner, Daniela Schuster, René de Vaumas, Khaled Alsabil, Stefan Lorkowski |
|---|---|
| Přispěvatelé: | Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Department of Pharmacology and Toxicology and Center for Molecular Biosciences Innsbruck (CMBI), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene isoform medicine.drug_class Garcinia kola Pharmaceutical Science 01 natural sciences Anti-inflammatory Analytical Chemistry Cell Line 03 medical and health sciences chemistry.chemical_compound Isomerism garcinoic acid Drug Discovery medicine semisynthesis Humans Benzopyrans tocotrienol Prostaglandin E2 Enzyme Inhibitors Garcinia IC50 Prostaglandin-E Synthases Pharmacology biology 010405 organic chemistry Plant Extracts Organic Chemistry mPGES-1 [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences biology.organism_classification Semisynthesis 0104 chemical sciences 030104 developmental biology Complementary and alternative medicine chemistry Biochemistry Plant Bark Molecular Medicine Tocotrienol medicine.drug |
| Zdroj: | Planta Medica Planta Medica, Georg Thieme Verlag, 2016, 82 (11/12), pp.1110-1116. ⟨10.1055/s-0042-108739⟩ |
| ISSN: | 1439-0221 0032-0943 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|