A class of novel mogrol derivatives modified on A ring were synthesized. The screening result showed that indole-fused derivatives exhibited lower toxicity and better anti-inflammatory activity in LPS-induced RAW 264.7 cells model than mogrol and other compounds. Derivative B8 exerted superior inhibitory result of NO production (IC₅₀ = 5.05 μM) and inhibitory ability of TNF-α and IL-6 secretion to mogrol through iNOS/NF-κB pathway. Besides, the CCK8 assay was performed to evaluate their anti-proliferative activity against non-small cell lung cancer including A549, NCI-H460, H1299 and H1975 cells. Compared with mogrol, compound B8 showed moderate anti-proliferative activities against A549 and H1975 cells, while derivatives bearing α, β-unsaturated ketone scaffold displayed broad-spectrum growth inhibition against four cell lines. Among them, compound A9 showed 12-fold higher activity than mogrol against H1299 and H1975 cells. The suppressive effect on expression level of p-p65 might account for the compound A9-induced growth inhibition and cell cycle arrest at G1 phase.

合成了一类在A环上修饰的新型莫洛尔衍生物。筛选结果表明，吲哚稠合衍生物在LPS诱导的RAW 264.7细胞模型中表现出比莫格罗等化合物更低的毒性和更好的抗炎活性。衍生物B8对 NO 产生（IC ₅₀  = 5.05 μM）和通过 iNOS/NF-κB 通路抑制 TNF-α 和 IL-6 分泌到 mogrol 具有优异的抑制效果。此外，进行CCK8测定以评估它们对包括A549、NCI-H460、H1299和H1975细胞在内的非小细胞肺癌的抗增殖活性。与莫洛尔相比，复方B8显示对 A549 和 H1975 细胞的中等抗增殖活性，而带有 α，β-不饱和酮支架的衍生物显示对四种细胞系的广谱生长抑制。其中，化合物A9对 H1299 和 H1975 细胞的活性比 mogrol 高 12 倍。对 p-p65 表达水平的抑制作用可能是化合物A9在 G1 期诱导的生长抑制和细胞周期停滞的原因。