College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules. 2018 Nov 22;23(12):3059. doi: 10.3390/molecules23123059.
Cytisine-pterocarpan-derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a ,-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B () was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound was evaluated against breast cancer cell lines and showed that had a better cytotoxicity against MDA-MB-231 cells (IC = 19.2 μM). Depending on the research on cytotoxicities of against RAW 264.7 and BV2 cells, it was suggested that produced low cytotoxic effects on the central nervous system. Further study indicated that demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.
采用（-）-野靛碱和（-）马卡因为原料，通过-4-二甲基-4-氨基吡啶（DMAP）介导的温和合成策略，仿生合成了野靛碱-紫檀烷类化合物。在本研究中，采用优化的反应条件，以良好和高产率制备了托品宁 B（）。对化合物进行了体外细胞毒性评价，结果表明，化合物对 MDA-MB-231 细胞具有更好的细胞毒性（IC=19.2μM）。根据对 RAW 264.7 和 BV2 细胞的毒性研究，表明化合物对中枢神经系统的毒性作用较低。进一步的研究表明，化合物对 MDA-MB-231 细胞表现出细胞毒性活性，细胞毒性活性是通过细胞凋亡诱导的。结果表明，细胞凋亡可能是通过调节 Bax/Bcl-2 比值和促进细胞色素 c 从线粒体向细胞质释放，通过线粒体介导的凋亡途径诱导的。
