Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle, Germany.
Bioorg Med Chem Lett. 2010 Jun 1;20(11):3409-12. doi: 10.1016/j.bmcl.2010.04.004. Epub 2010 Apr 18.
Synthesis and antiproliferative activity of eight new derivatives of betulinic acid (1) and betulin (2) are described. The compounds were tested against fifteen tumor cell lines. The toxicity against normal human fibroblasts and the mode of cell death on lung cancer cell line induced by the most active compounds 9 (bis(ethylcarbamate)betulin) and 11 (3-O-ethylcarbamate of 28-O-acetylbetulin) was investigated. Caspase 3 activity on lung cancer cell line (A549) was determined for 1, 5 (3-O-ethylcarbamate of betulinic acid), 9 and 11. All derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of lung cancer cells for 24h with 9 and 11 induced apoptosis, as observed by the appearance of a typical ladder pattern in the DNA fragmentation assay.
描述了白桦脂酸（1）和白桦醇（2）的 8 种新衍生物的合成及抗增殖活性。测试了这些化合物对 15 种肿瘤细胞系的活性。研究了毒性对正常人类成纤维细胞的影响，以及最活跃的化合物 9（双（乙基氨基甲酸酯）白桦醇）和 11（28-O-乙酰基白桦醇的 3-O-乙基氨基甲酸酯）对肺癌细胞系诱导的细胞死亡方式。对肺癌细胞系（A549）测定了化合物 1、5（白桦脂酸的 3-O-乙基氨基甲酸酯）、9 和 11 的半胱天冬酶 3 活性。所有衍生物在微摩尔浓度下对靶肿瘤细胞系均表现出剂量依赖性的抗增殖作用。用 9 和 11 处理肺癌细胞 24 小时可诱导细胞凋亡，如 DNA 片段化分析中出现典型梯状模式所观察到的。
