Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, P. R. China.
Chem Biodivers. 2022 Aug;19(8):e202200372. doi: 10.1002/cbdv.202200372. Epub 2022 Aug 8.
Based on the well-known cytotoxicity of indole compounds, we used the 'Fisher indole synthesis' method to introduce appropriately substituted indole rings into panaxadiol (PD), generating eighteen novel Panaxadiol indole derivatives. Six human cancer cell lines (A549, HepG-2, HCT-116, SGC-7901, MDA-MB-231, PC-3 cells) and one normal ovarian cell lines (IOSE144) were designed to evaluate the anti-proliferative activity of the PD derivatives. The results showed that the majority of PD derivatives showed enhanced anti-proliferative activity, when compared with PD, with P-Methylindolo-PD exhibiting the highest cytotoxicity. In A549 cells, IC value was 5.01±0.87 μM, which is roughly 12 times higher than the activity of PD and 5 times that of 5-FU. Moreover, cell morphology analysis and Annexin V-FITC/PI assays exhibited that P-Methylindolo-PD could induce A549 cell apoptosis (55.7 % of apoptotic cells at 20 μM). Moreover, molecular docking experiments were performed to explore the molecular mechanism underlining the binding of P-Methylindolo-PD to the active site of EGFR. The results support that P-Methylindolo-PD might be a promising lead compound for further studies.
基于吲哚类化合物的众所周知的细胞毒性，我们使用“Fisher 吲哚合成”方法将适当取代的吲哚环引入人参二醇（PD）中，生成了十八种新的人参二醇吲哚衍生物。六种人类癌细胞系（A549、HepG-2、HCT-116、SGC-7901、MDA-MB-231、PC-3 细胞）和一种正常卵巢细胞系（IOSE144）被设计用来评估 PD 衍生物的抗增殖活性。结果表明，与 PD 相比，大多数 PD 衍生物表现出增强的抗增殖活性，其中 P-甲基吲哚-PD 表现出最高的细胞毒性。在 A549 细胞中，IC 值为 5.01±0.87 μM，约为 PD 活性的 12 倍，是 5-FU 的 5 倍。此外，细胞形态分析和 Annexin V-FITC/PI 检测表明，P-甲基吲哚-PD 可以诱导 A549 细胞凋亡（20 μM 时凋亡细胞为 55.7%）。此外，还进行了分子对接实验，以探索 P-甲基吲哚-PD 与 EGFR 活性位点结合的分子机制。结果支持 P-甲基吲哚-PD 可能是进一步研究的有前途的先导化合物。
