Synthesis and Biological Evaluation of Isoaurone Derivatives as Anti-inflammatory Agents.

Twenty-eight isoaurone derivatives with 1,2,4-triazole moieties were synthesized using a fragment-based design strategy, and their anti-inflammatory activity was investigated. The anti-inflammatory effect of the most active derivative, 14e (41.82 %), was dose-dependent and higher than the values for celecoxib (31.82 %). Compound 14e was almost non-toxic and inhibited different concentrations of nitric oxide (NO). The western blotting results demonstrated that cyclooxygenase-2 (COX-2) expression was elevated when the macrophages were exclusively treated with LPS. However, compound 14e effectively suppressed the LPS-induced COX-2 upregulation. Subsequent investigation revealed that 14e is a promising compound capable of inhibiting the downstream signaling of COX-2. With the above interesting biological profile, molecular 14e could be a promising lead to develop novel anti-inflammatory agents.