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Isomeric 3-Pyridinylmethylcoumarins Differ in Erk1/2-Inhibition and Modulation of BV2 Microglia-Mediated
Rami Schulzki1, Matthias Apweiler1, Caroline Röttger2
1Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, D-79104 Freiburg, Germany.
Abstract:
Coumarins are known for their multiple biological effects and have been established as anti-coagulative drugs for years. Furthermore, some coumarins can promote anti-inflammatory effects via the GPR55 receptor, and dual target coumarins have been synthesized. Anti-inflammatory drugs might be beneficial in the treatment of neuropsychiatric disorders, as the inflammatory hypothesis suggests. For the current study, we compared isomeric 3-pyridinylmethylcoumarins with altered N-atom position regarding their effects on cytokine and chemokine synthesis and expression in LPS-stimulated BV2 microglial cells. The 3-pyridin-4-yl-methylcoumarin showed the most potent anti-inflammatory effects, followed by the 3-pyridin-2-ylmethylcoumarin analog. The observed effects might be mediated by an inhibition of ERK phosphorylation.
