Discovery, Topo I inhibitory activity and mechanism evaluation of two novel cytisine-type alkaloid dimers from the seeds of Sophora alopecuroides L

Abstract

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.