Cytisine-Pterocarpan-Derived Compounds: Biomimetic Synthesis and Apoptosis-Inducing Activity in Human Breast Cancer Cells

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 12; p. 3059
• Main Authors: Peng, Ting-Ting, Sun, Xuan-Rong, Liu, Ren-Hao, Hua, Lu-Xia, Cheng, Dong-Ping, Mao, Bin, Li, Xing-Nuo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.11.2018; MDPI
• Subjects: Alkaloids - chemistry; Animals; Apoptosis; Azocines - chemistry; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Biological Mimicry; Biomimetic materials; biomimetic synthesis; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Central nervous system; cytisine-pterocarpan derived compounds; Cytochrome; Cytochrome c; Cytochromes c - metabolism; Cytoplasm; Cytotoxicity; Female; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - pharmacology; Humans; MCF-7 Cells; Mice; Mitochondria - metabolism; mitochondrion-mediated apoptosis; Molecular Structure; Nervous system; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Pterocarpans - chemistry; Quinolizines - chemistry; RAW 264.7 Cells; Solvents; Tumor cell lines; China; cytisine-pterocarpan derived compounds; breast cancer; mitochondrion-mediated apoptosis; biomimetic synthesis
• ISSN: 1420-3049; 1420-3049
• 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.