Abstract

Carabrol, isolated from Carpesium macrocephalum Franch. & Sav., showed anti-inflammatory potential in LPS-induced RAW264.7 murine macrophages. We transformed the structure of carabrol and modified the carbon atoms at positions 11 and 13 to obtain a series of carabrol derivatives. The anti-inflammatory activity of 26 carabrol derivatives was synthesized and screened. Their structures were established using 1H NMR, 13C NMR, and HRMS spectroscopic data. All compounds were tested against RAW264.7 cells using the Griess assay; the bioassay test suggested that most of the compounds were found to have in vitro anti-inflammatory activities with low cytotoxicity. We identified several novel carabrol derivatives, which have potent anti-inflammatory activities for tested RAW264.7 cells with IC50 values that ranged from 0.82 to 1.31 μM. Among these, compound a9 was identified as the most potent anti-inflammatory agent, effectively suppressing key pro-inflammatory mediators such as nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In a xylene-induced ear swelling model in mice, compound a9 demonstrated a significant inhibitory effect on ear swelling, highlighting its potent in vivo anti-inflammatory activity.