State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, Republic of China.
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, Republic of China.
Bioorg Chem. 2024 Nov;152:107739. doi: 10.1016/j.bioorg.2024.107739. Epub 2024 Aug 22.
Thirty-two diterpenoids including 18 ent-kauranes (1-6, and 12-23), nine 8,9-seco-ent-kauranes (7-8, and 24-30), four ent-abietanes (9-10, and 31-32), and one crotofolane (11) were isolated from the twigs and leaves of Croton kongensis. The structures of previously unreported crokokaugenoids A-H (1-8), crokoabiegenoids A-B (9-10), and crokocrotogenoid A (11) were determined by spectroscopic data analyses, TDDFT-ECD and GIAO NMR calculations, and X-ray crystallographic studies. All compounds were evaluated for their cytotoxic activity against five human tumor cell lines, and the structure-activity relationships were discussed. Biological tests exhibited that compound 1 possessed strong anti-proliferation activity, arrested cell cycle at G2/M phase, and induced cell apoptosis of MDA-MB-231. The mechanism investigation showed that compound 1 can inhibit tumor proliferation and migration by targeting mitochondria to increase intracellular reactive oxygen species (ROS) and regulating STAT3 and FAK signal pathways. Collectively, these findings supported the great potential of compound 1 as a hopeful anticancer agent.
从贵州产的克罗藤中分离得到了 32 个二萜类化合物，包括 18 个贝壳杉烷（1-6 和 12-23），9 个 8,9-裂贝壳杉烷（7-8 和 24-30），4 个贝壳杉烷（9-10 和 31-32）和 1 个克罗托烷（11）。通过光谱数据分析、TDDFT-ECD 和 GIAO NMR 计算以及 X 射线晶体学研究，确定了以前未报道的克罗考根烷 A-H（1-8）、克罗考比根烷 A-B（9-10）和克罗考克罗托烷 A（11）的结构。所有化合物都对五种人肿瘤细胞系进行了细胞毒性活性评价，并讨论了构效关系。生物试验表明，化合物 1 具有很强的抗增殖活性，可将细胞周期阻滞在 G2/M 期，并诱导 MDA-MB-231 细胞凋亡。机制研究表明，化合物 1 可以通过靶向线粒体增加细胞内活性氧（ROS）并调节 STAT3 和 FAK 信号通路来抑制肿瘤增殖和迁移。综上所述，这些发现支持化合物 1 作为有希望的抗癌药物的巨大潜力。
