A series of inhibitors of NF-κB based on ursolic acid (UA) derivatives containing long-chain diamine moieties were designed and synthesized as well as evaluated the antitumor effects. These compounds exhibited significant inhibitory activity to the NF-κB with IC₅₀ values at micromolar concentrations in A549 lung cancer cell line. Among them, compound 8c exerted potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC₅₀ values ranged from 5.22 to 8.95 μM. Moreover, compound 8c successfully suppressed the migration of A549 cells. Related mechanism study indicated compound 8c caused cell cycle arrest at G1 phase and triggered apoptosis in A549 cells through blockage of NF-κB signalling pathway. Molecular docking study revealed that key interactions between 8c and the active site of NF-κB in which the bulky and strongly electrophilic group of long-chain diamine moieties were important for improving activity.

设计并合成了一系列基于含有长链二胺基团的熊果酸（UA）衍生物的NF-κB抑制剂，并评估了其抗肿瘤作用。这些化合物以微摩尔浓度在A549肺癌细胞系中表现出对NF-κB的显着抑制活性，IC ₅₀值为。其中，化合物8c对包括多药耐药性人类癌症系在内的测试肿瘤细胞系发挥有效活性，IC ₅₀值在5.22至8.95μM的范围内。此外，化合物8c成功抑制了A549细胞的迁移。相关机理研究表明化合物8c通过阻断NF-κB信号通路，导致细胞周期停滞在G1期并触发A549细胞凋亡。分子对接研究表明8c与NF-κB活性位点之间的关键相互作用，其中长链二胺部分的庞大且强亲电基团对于提高活性很重要。