Yang Sheng-Jie, Liu Ming-Chuan, Zhao Qi, Hu De-Yu, Xue Wei, Yang Song
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China; Research Institute, Sinphar Tian-Li Pharmaceutical Co., Ltd, Hangzhou 311100, PR China; Research Institute of Traditional Chinese Medicine, Yangtze River Pharmaceutical Group Co., Ltd, Taizhou 225321, PR China.
State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China; Research Institute, Sinphar Tian-Li Pharmaceutical Co., Ltd, Hangzhou 311100, PR China.
Eur J Med Chem. 2015;96:58-65. doi: 10.1016/j.ejmech.2015.04.006. Epub 2015 Apr 4.
Structural modification was performed at the C-28 position of betulonic acid (BetA). Twenty-five BetA derivatives were synthesized, and evaluated for their antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines by MTT assay. Among the derivatives, most of the derivatives had significant antiproliferative ability (IC50 < 19 μM). Compound 3k, the most active compound, showed IC50 values of 3.6, 5.6, 4.2, 7.8, and 5.2 μM on the five cancer cell lines respectively, and was selected to investigate cell apoptosis by subsequent florescence staining and flow cytometry analysis. The results revealed that compound 3k could induce apoptosis in MGC-803 cell lines, and the apoptosis ratios reached 28.33% after 36 h of treatment at 10 μM. In addition, the study of cancer cell apoptotic signaling pathway indicated that the apoptosis of MGC-803 cells induced by compound 3k could be through the mitochondrial intrinsic pathway.
在桦木酸（BetA）的C-28位进行了结构修饰。合成了25种BetA衍生物，并通过MTT法评估了它们对MGC-803、PC3、Bcap-37、A375和MCF-7人癌细胞系的抗肿瘤活性。在这些衍生物中，大多数衍生物具有显著的抗增殖能力（IC50 < 19 μM）。活性最强的化合物3k在这五种癌细胞系上的IC50值分别为3.6、5.6、4.2、7.8和5.2 μM，并被选用于后续的荧光染色和流式细胞术分析来研究细胞凋亡。结果表明，化合物3k可诱导MGC-803细胞系凋亡，在10 μM处理36小时后凋亡率达到28.33%。此外，对癌细胞凋亡信号信号通路的研究表明，化合物3k诱导的MGC-803细胞凋亡可能通过线粒体内在途径。
