Anti-neuroinflammatory potential of hydroxybenzoic ester derivatives: In silico insight and in vitro validation

Abstract

This study explores the anti-neuroinflammatory and antioxidant potential of 42 hydroxybenzoic acid esters and three parent acids. Molecular docking simulations targeted key proteins involved in the lipopolysaccharide (LPS) signaling pathway to identify lead compounds for synthesis and in vitro evaluation. Among the screened esters, the most promising candidates demonstrated antioxidant activity comparable to vitamin C in ABTS and DPPH assays. Additionally, these esters significantly reduced the production of reactive oxygen species (ROS) and nitric

oxide (NO) in H2O2- and LPS-stimulated BV2 microglial cells, indicating their ability to attenuate neuro- inflammation. Further testing in SH-SY5Y neuronal cells exposed to microglia-derived supernatants confirmed

the neuroprotective effects of these esters, reducing microglia-mediated neurotoxicity. These results suggest that

hydroxybenzoic acid ester derivatives are promising candidates for mitigating microglia-driven neuro- inflammation and protecting neurons, offering potential therapeutic applications for neurodegenerative diseases.