Design, synthesis, and biological evaluation of novel heteroaryl, squaramide, and indolcarboxamide derivatives as formyl peptide receptor 2 agonists to target neuroinflammation

Formyl Peptide Receptor 2 (FPR2) is a G protein–coupled receptor involved in the resolution phase of inflammation and represents a promising therapeutic target for neuroinflammatory disorders such as Alzheimer’s disease and autism spectrum disorder. The aim of this study was to evaluate the anti-inflammatory and pro-resolving effects of selected FPR2 agonists with hydrogen sulfide (H₂S)-releasing properties in an in vitro model of neuroinflammation. The dataset includes experimental data obtained from primary murine microglial cultures under basal conditions and following lipopolysaccharide (LPS) stimulation. Moreover, the specificity of the observed effects was assessed by pretreating primary microglial cells with the selective FPR2 antagonist WRW4.The collection comprises processed data from biochemical assays, including cytokine levels (ELISA), nitric oxide production (Griess assay), and cytotoxicity (LDH assay), allowing assessment of microglial activation and inflammatory response.The results demonstrate that the tested compounds attenuate LPS-induced cytotoxicity and modulate inflammatory signaling by reducing the levels of pro-inflammatory cytokines and normalizing anti-inflammatory responses in microglial cells.