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Targeting oxidative stress: Novel coumarin-based inverse agonists of GPR55

Apweiler, Matthias; Saliba, Soraya Wilke; Streyczek, Jana; Hurrle, Thomas; Gräßle, Simone; Bräse, Stefan; Fiebich, Bernd L.


Oxidative stress is associated with different neurological and psychiatric diseases. Therefore, development of new pharmaceuticals targeting oxidative dysregulation might be a promising approach to treat these diseases. The G-protein coupled receptor 55 (GPR55) is broadly expressed in central nervous tissues and cells and is involved in the regulation of inflammatory and oxidative cell homeostasis. We have recently shown that coumarin-based compounds enfold inverse agonistic activities at GPR55 resulting in the inhibition of prostaglandin E2. However, the antioxidative effects mediated by GPR55 were not evaluated yet. Therefore, we investigated the antioxidative effects of two novel synthesized coumarin-based compounds, KIT C and KIT H, in primary mouse microglial and human neuronal SK-N-SK cells. KIT C and KIT H show antioxidative properties in SK-N-SH cells as well as in primary microglia. In GPR55-knockout SK-N-SH cells, the antioxidative effects are abolished, suggesting a GPR55-dependent antioxidative mechanism. Since inverse agonistic GPR55 activation in the brain seems to be associated with decreased oxidative stress, KIT C and KIT H possibly act as inverse agonists of GPR55 eliciting promising therapeutic options for oxidative stress related diseases.

Verlagsausgabe §
DOI: 10.5445/IR/1000139734
Veröffentlicht am 12.11.2021
DOI: 10.3390/ijms222111665
Zitationen: 4
Web of Science
Zitationen: 4
Zitationen: 4
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Institut für Organische Chemie (IOC)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 28.10.2021
Sprache Englisch
Identifikator ISSN: 1661-6596, 1422-0067
KITopen-ID: 1000139734
HGF-Programm 43.33.11 (POF IV, LK 01) Adaptive and Bioinstructive Materials Systems
Erschienen in International Journal of Molecular Sciences
Verlag MDPI
Band 22
Heft 21
Seiten Art.Nr. 11665
Nachgewiesen in Web of Science
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