Most clinical drugs used to treat inflammation have serious gastrointestinal, renal, and cardiovascular side effects during long-term treatment. The development of new anti-inflammatory agents from natural products and their derivatives is a powerful approach to overcome these adverse effects. Batatasin III, a bibenzyl natural product, has been found to have anti-inflammatory activity. Compared with other anti-inflammatory agents, batatasin III has a simple and unique structure. Therefore, batatasin III and its analogs might have the potential to treat inflammation with only mild adverse effects as a new type of anti-inflammatory agent. Herein, we synthesized 26 batatasin III analogs and evaluated the anti-inflammatory activity in vitro. Analog 21 significantly inhibited (p < 0.01) nitric oxide production with an IC₅₀ value of 12.95 μM. Western blot analysis further revealed that 21 reduced iNOS, phosphorylated p65, and β-catenin expression in a concentration-dependent manner. These results indicated that 21 could be a potential lead compound for developing a drug candidate for ulcerative colitis. Molecular docking analysis showed that p65 might be a potential target of 21 for the treatment of inflammatory disease. In addition, we analyzed the structure–activity relationship of the analogs, which provides a basis for future structural modifications.

临床上大多数用于治疗炎症的药物在长期治疗过程中都会产生严重的胃肠道、肾脏和心血管副作用。从天然产物及其衍生物中开发新的抗炎剂是克服这些副作用的有效方法。Batatasin III 是一种联苄基天然产物，已被发现具有抗炎活性。与其他抗炎药相比，batatasin III 具有简单而独特的结构。因此，batatasin III及其类似物作为一种新型抗炎药可能具有治疗炎症且副作用轻微的潜力。在此，我们合成了26种batatasin III类似物并评估了体外抗炎活性。类似物21显着抑制 (p < 0.01) 一氧化氮的产生，IC ₅₀值为 12.95 μM。Western blot 分析进一步表明，21以浓度依赖性方式降低 iNOS、磷酸化 p65 和 β-catenin 的表达。这些结果表明21可能是开发溃疡性结肠炎候选药物的潜在先导化合物。分子对接分析表明p65可能是21治疗炎症性疾病的潜在靶点。此外，我们还分析了类似物的构效关系，为未来的结构修饰提供了基础。