Chen Yecang, Zhu Feifei, Ding Yuxin, Xing Lin, Wang Enxiao, Fang Yixiang, Sheng Ruilong, Tu Qidong, Guo Ruihua
Division of Biomedical Engineering, James Watt School of Engineering, University of Glasgow, Glasgow G12 8LT, UK.
College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China.
Biomedicines. 2025 Mar 25;13(4):793. doi: 10.3390/biomedicines13040793.
Isosteviol, a tetracyclic diterpenoid with a beyerene-type skeleton, exhibited wide pharmacological activities and an inhibitory impact on tumor proliferation in colon cancer; 22 isosteviol derivatives were synthesized by modifying the C-16 and C-19 position of isosteviol, and then the inhibitory activities of derivatives - were evaluated by CCK8 method. Next, the structure-activity relationships (SARs) of these isosteviol derivatives in HCT116 cells were discussed in detail. Network pharmacology was employed to predict and analyze the targets of isosteviol in the treatment of colon cancer; The results indicated derivative possessed stronger inhibitory activity against HCT116 and HepG2 cells (IC = 6.20 ± 0.61 μM for HCT116, and IC = 39.84 ± 0.43 μM for HepG2). Additionally, cell cycle analysis indicated that derivative arrested HCT116 cells at the G1 phase and increased the percentage of apoptotic cells. Moreover, the molecular docking showed that derivative could interact with TP53 through its Tyr-1600 and Leu-1534 residues (docking energy: -11.84 kcal/mol); With these results, we can conclude that derivative may be a promising candidate for anticancer chemotherapy.
异甜菊醇是一种具有贝壳杉烯型骨架的四环二萜，具有广泛的药理活性，对结肠癌肿瘤增殖有抑制作用；通过修饰异甜菊醇的C-16和C-19位合成了22种异甜菊醇衍生物，然后用CCK8法评估衍生物的抑制活性。接下来，详细讨论了这些异甜菊醇衍生物在HCT116细胞中的构效关系（SARs）。采用网络药理学预测和分析异甜菊醇治疗结肠癌的靶点；结果表明，衍生物对HCT116和HepG2细胞具有更强的抑制活性（对HCT116的IC = 6.20±0.61μM，对HepG2的IC = 39.84±0.43μM）。此外，细胞周期分析表明，衍生物使HCT116细胞停滞在G1期并增加凋亡细胞的百分比。而且，分子对接表明，衍生物可以通过其Tyr-1600和Leu-1534残基与TP53相互作用（对接能量：-11.84 kcal/mol）；基于这些结果，我们可以得出结论，衍生物可能是抗癌化疗的一个有前途的候选药物。
