Pham Thi-Anh, Shair Mohammad Imran, Vu Van-Tuan, Hu Xiao-Long, Birendra Chaurasiya, Ulah Aftab, Guo Cui, Lü Xian-Yu, Ye Wen-Cai, Wang Hao
State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, P. R. China.
Chem Biodivers. 2018 Jun;15(6):e1800052. doi: 10.1002/cbdv.201800052. Epub 2018 May 21.
A new phloroglucinol derivative, named eucalyptin B (1), along with five related known compounds (2 - 6), was isolated from the fruits of Eucalyptus globulus. Their structures were elucidated by means of 1D- and 2D-NMR spectroscopy, with the absolute configuration of 1 determined by electronic circular dichroism (ECD) calculations. All isolated compounds (1 - 6) were evaluated for their cytotoxic activities against lung (A549), breast (4T1), and skin (B16F10) cancer cell lines. On the basis of cell viability assay, the cytotoxic activity of eucalyptin B (1) was further confirmed by apoptosis assay. Additionally, after treatment with eucalyptin B (1), the apoptosis factor proteins (Bcl2 and Bax) and caspase-3 levels in A549 cells were also determined by Western-blot analysis. By cytotoxic assay, eucalyptin B (1) exhibited potent cytotoxicity against A549 cells with an IC value of 1.51 μm and induced concentration dependent apoptosis of up to 49%. Additionally, eucalyptin B (1) inhibited 5-fold and increased 10-folds in the level of Bcl2 and Bax, respectively. Furthermore, the 11-fold increase in the level of caspase-3 confirmed eucalyptin B (1) activated caspase dependent apoptosis pathway. In conclusion, the isolated compound eucalyptin B (1) has promising cytotoxic activity in tumor cells, especially in A549.
从蓝桉果实中分离出一种新的间苯三酚衍生物，命名为桉叶素B（1），以及五种相关的已知化合物（2 - 6）。通过一维和二维核磁共振光谱对其结构进行了阐明，通过电子圆二色性（ECD）计算确定了1的绝对构型。对所有分离出的化合物（1 - 6）针对肺癌（A549）、乳腺癌（4T1）和皮肤癌（B16F10）细胞系的细胞毒性活性进行了评估。基于细胞活力测定，通过凋亡测定进一步证实了桉叶素B（1）的细胞毒性活性。此外，在用桉叶素B（1）处理后，还通过蛋白质免疫印迹分析测定了A549细胞中凋亡因子蛋白（Bcl2和Bax）以及半胱天冬酶 - 3的水平。通过细胞毒性测定，桉叶素B（1）对A549细胞表现出强大的细胞毒性，IC值为1.51μm，并诱导高达49%的浓度依赖性凋亡。此外，桉叶素B（1）分别使Bcl2水平降低5倍和使Bax水平升高10倍。此外，半胱天冬酶 - 3水平升高11倍证实了桉叶素B（1）激活了半胱天冬酶依赖性凋亡途径。总之，分离出的化合物桉叶素B（1）在肿瘤细胞中具有有前景的细胞毒性活性，尤其是在A549细胞中。
