Carbamate derivatives of betulinic acid and betulin with selective cytotoxic activity
Carbamate derivatives of betulinic acid and betulin with selective cytotoxic activity
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DOI：
10.1016/j.bmcl.2010.04.004
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发表时间：
2010-06-01
影响因子：
2.7
通讯作者：
Paschke, Reinhard
中科院分区：
文献类型：
--
作者：
Kommera, Harish;Kaluderovic, Goran N.;Paschke, Reinhard
报道了桦木酸（1）和桦木醇（2）的八个新衍生物的合成及其抗肿瘤活性。针对15种肿瘤细胞系测试化合物。本文研究了活性最高的化合物9（二（乙基氨基甲酸酯）白桦脂醇）和11（28-O-乙酰白桦脂醇的3-O-乙基氨基甲酸酯）对正常人成纤维细胞的毒性和对肺癌细胞系的细胞死亡方式。测定1、5（桦木酸的3-O-乙基氨基甲酸酯）、9和11对肺癌细胞系（A549）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抗增殖作用。用9和11处理肺癌细胞24小时诱导细胞凋亡，如通过DNA片段化测定中典型的梯形图的出现所观察到的。(C)2010爱思唯尔有限公司版权所有。
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 24 h with 9 and 11 induced apoptosis, as observed by the appearance of a typical ladder pattern in the DNA fragmentation assay. (C) 2010 Elsevier Ltd. All rights reserved.