Meng Chenting, Wang Yanqing, Chen Shengxue, Li Min, Yuan Chunping, Yin Xiaoying
School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China.
School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China; Shanghai Engineering Research Center for Pharmaceutical Intelligent Equipment, Shanghai University of Engineering Science, Shanghai 201620, China.
Bioorg Med Chem. 2022 May 1;61:116723. doi: 10.1016/j.bmc.2022.116723. Epub 2022 Mar 26.
Alopecurosines A and B (CMs 1 and 2, respectively) are two novel cytisine-type alkaloid dimers first isolated from the aerial parts of Sophora alopecuroides L. CMs 1 and 2 are new dimeric alkaloids whose piperidine matrine ring is cleaved and connected via the N'-1 bond. Their chemical structures have been confirmed by IR, UV, HR-ESI-MS, and NMR. Preliminary screening shows that they have topoisomerase I (Topo I)-based anti-tumor activity. Their Topo I inhibitory activities and mechanism have been evaluated by agarose gel electrophoresis assay and a molecular docking study. The results show that the inhibition rate of CM 1 is 82.26% at 1 mM concentration and that it exhibits significantly Topo I inhibitory activity. Further research has illustrated that CMs 1 and 2 exert inhibitory activity by stabilising the Topo I-DNA cleavage complex, implying that they have the potential to be developed as novel Topo I inhibitors.
苦马豆素A和B（分别为化合物1和2）是两种新型的金雀花碱型生物碱二聚体，首次从苦马豆的地上部分分离得到。化合物1和2是新的二聚体生物碱，其哌啶苦参碱环断裂并通过N'-1键连接。它们的化学结构已通过红外光谱（IR）、紫外光谱（UV）、高分辨电喷雾电离质谱（HR-ESI-MS）和核磁共振（NMR）得以确证。初步筛选表明，它们具有基于拓扑异构酶I（Topo I）的抗肿瘤活性。通过琼脂糖凝胶电泳分析和分子对接研究对它们的Topo I抑制活性及其作用机制进行了评估。结果表明，在1 mM浓度下，化合物1的抑制率为82.26%，且表现出显著的Topo I抑制活性。进一步的研究表明，化合物1和2通过稳定Topo I-DNA切割复合物发挥抑制活性，这意味着它们有潜力被开发成为新型的Topo I抑制剂。
