Alopecuroidines A−C, three matrine-derived alkaloids from the seeds of Sophora alopecuroides

Three matrine-derived alkaloids, alopecuroidine A (1), alopecuroidine B (2a) and alopecuroidine C (2b) were isolated from the seeds of Sophora alopecuroides. Their structures were elucidated by extensive spectroscopic analyses and X-ray diffraction. Three compounds possess an unprecedented rearranged fused 7/6/5/6 tetracyclic skeleton with a diazacycloheptane structure. Their plausible biosynthetic pathway was also proposed. The anti-proliferative activities of compounds 1 and 2a were examined by the MTT assay. Compound 1 inhibited the viability of human lung cancer A549 cells, having a half maximal inhibitory concentration (IC50) of 7.58 ± 2.47 μmol/L at 72 h. The flow cytometric analysis suggested that 1 inhibited A549 cell growth by inducing apoptosis and cell-cycle arrest. Additionally, 1 induced the loss of mitochondrial membrane potential, elevated intracellular reactive oxygen species, increased the Bax/Bcl-2 ratio, stimulated cleaved-caspase-3 and P53 protein levels, and suppressed the pro-caspase-3 level. Thus, 1 appeared to induce A549 cells apoptosis through a mitochondria-mediated apoptotic pathway.