Bai Xueqian, Ye Chao, Liu Zhe, Zhou Zhijiang, Zhang Tianyi
Jilin Medical University, Jilin, 132013, PR China.
Chem Biodivers. 2025 Mar;22(3):e202402073. doi: 10.1002/cbdv.202402073. Epub 2024 Nov 13.
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.
采用基于片段的设计策略合成了28种带有1,2,4-三唑部分的异黄酮衍生物，并对其抗炎活性进行了研究。活性最高的衍生物14e的抗炎效果（41.82%）呈剂量依赖性，且高于塞来昔布（31.82%）。化合物14e几乎无毒，并能抑制不同浓度的一氧化氮（NO）。蛋白质印迹结果表明，当巨噬细胞仅用脂多糖（LPS）处理时，环氧合酶-2（COX-2）的表达会升高。然而，化合物14e有效地抑制了LPS诱导的COX-2上调。随后的研究表明，14e是一种有前景的化合物，能够抑制COX-2的下游信号传导。基于上述有趣的生物学特性，分子14e有望成为开发新型抗炎药物的先导化合物。
