Synthesis and biological evaluation of carabrol derivatives

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.