# Isomeric 3-Pyridinylmethylcoumarins Differ in Erk1/2-Inhibition and Modulation of BV2 Microglia-Mediated Neuroinflammation

## TL;DR

This study compares isomeric coumarins to see how they affect inflammation in brain cells, finding that one is more effective at reducing inflammation.

## Contribution

The study reveals how the position of the N-atom in isomeric coumarins affects their anti-inflammatory potency and ERK inhibition.

## Key findings

- 3-pyridin-4-yl-methylcoumarin showed the strongest anti-inflammatory effects in BV2 microglial cells.
- ERK phosphorylation inhibition may mediate the anti-inflammatory effects of these coumarins.
- The 3-pyridin-2-ylmethylcoumarin analog was less effective than the 4-yl isomer.

## 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.