Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents
Glycosidation of lupane-type triterpenoids as potent in vitro cytotoxic agents
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DOI：
10.1016/j.bmc.2006.05.075
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发表时间：
2006-10-01
影响因子：
3.5
通讯作者：
Pichette, Andr
中科院分区：
文献类型：
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作者：
Gauthier, Charles;Legault, Jean;Pichette, Andr
桦木酸 (3) 的弱水溶性阻碍了这种天然抗癌剂的临床开发。为了解决这个问题并增强桦木酸 (3) 和羽扇豆烷型三萜羽扇豆醇 (1)、桦木脑 (2) 和桦木酸甲酯 (7) 的药理特性，合成了苷类（β-D-葡萄糖苷、α-L-鼠李糖苷和 α-D-阿拉伯糖苷）并进行了体外测试 针对三种癌性细胞系（A-549、DLD-1 和 B16-F1）和一种健康细胞系（WS1）的细胞毒性。在桦木醇 (2) 的 C-3 或 C-28 位置添加糖部分会导致细胞毒性丧失。相比之下，羽扇豆醇 (1) 的 3-O-β-D-葡萄糖苷化将活性提高了 7 至 12 倍（IC50 14-15.0 mu M）。此外，结果表明，癌细胞系对桦木酸的3-O-α-L-吡喃鼠李糖苷衍生物的敏感性（IC50 2.6-3.9μM，22）比健康细胞（IC50 31μM）高8至12倍。因此，这项研究表明羽扇豆烷型三萜类化合物的 3-O-糖苷代表了一类令人感兴趣的有效体外细胞毒剂。 (c) 2006 Elsevier Ltd. 保留所有权利。
The weak hydrosolubility of betulinic acid (3) hampers the clinical development of this natural anticancer agent. In order to circumvent this problem and to enhance the pharmacological properties of betulinic acid (3) and the lupane-type triterpenes lupeol (1), betulin (2), and methyl betulinate (7), glycosides (beta-D-glucosides, alpha-L-rhamnosides, and alpha-D-arabinosides) were synthesized and in vitro tested for cytotoxicity against three cancerous (A-549, DLD-1, and B16-F1) and one healthy (WS1) cell lines. The addition of a sugar moiety at the C-3 or C-28 position of betulin (2) resulted in a loss of cytotoxicity. In contrast, the 3-O-beta-D-glucosidation of lupeol (1) improved the activity by 7- to 12-fold (IC50 14-15.0 mu M). Moreover, the results showed that cancer cell lines are 8- to 12-fold more sensitive to the 3-O-alpha-L-rhamnopyranoside derivative of betulinic acid (IC50 2.6-3.9 mu M, 22) than the healthy cells (IC50 31 mu M). Thus, this study indicates that 3-O-glycosides of lupane-type triterpenoids represent an interesting class of potent in vitro cytotoxic agents. (c) 2006 Elsevier Ltd. All rights reserved.