2-羟基-1,2-二氢山油柑碱糖苷的合成及其抗增殖活性
Synthesis and anti-proliferative activity of 2-hydroxy-1,2-dihydroacronycine glycosides.
作者信息
Mitaku S, Skaltsounis A L, Tillequin F, Koch M, Rolland Y, Pierré A, Atassi G
机构信息
Département de Pharmacie, Université d'Athènes, Greece.
出版信息
Pharm Res. 1996 Jun;13(6):939-43. doi: 10.1023/a:1016073700344.
PURPOSE
Combination of the acronycine pharmacophore with various sugar units appeared of interest, since numerous anticancer agents possess a sugar moiety, which strongly influence both their bioavailability and their selective toxicity towards tumor cells.
METHODS
A series of 2-hydroxy-1,2-dihydroacronycine glycosides were synthetized, by condensation of the racemic aglycone with appropriate glycoside donors. Their effect on the inhibition of L1210 cell proliferation were evaluated.
RESULTS
Compounds 6a, 6b, 11a, 11b, and 12a, 12b, including a halogenated sugar moiety displayed activities of the same order of magnitude as acronycine itself. Compounds 7a, 7b, and 8a, 8b, bearing a 2.3.6-trideoxy-3-azido-L-lyxo- and L-arabino-hexopyranose unit respectively, were significantly more potent than acronycine in inhibiting cell proliferation.
CONCLUSIONS
The activity of 2-hydroxy-1,2-dihydroacronycine glycosides seems to be related to the lipophilicity of the sugar unit.
目的
鉴于众多抗癌药物都含有糖部分，而糖部分对其生物利用度和对肿瘤细胞的选择性毒性都有强烈影响，因此将阿克罗宁药效基团与各种糖单元结合显得很有意义。
方法
通过外消旋苷元与合适的糖苷供体缩合，合成了一系列2-羟基-1,2-二氢阿克罗宁糖苷。评估了它们对L1210细胞增殖的抑制作用。
结果
化合物6a、6b、11a、11b以及12a、12b，包括一个卤代糖部分，显示出与阿克罗宁本身相同数量级的活性。分别带有2,3,6-三脱氧-3-叠氮基-L-来苏糖基和L-阿拉伯糖基己吡喃糖单元的化合物7a、7b以及8a、8b，在抑制细胞增殖方面比阿克罗宁显著更有效。
结论
2-羟基-1,2-二氢阿克罗宁糖苷的活性似乎与糖单元的亲脂性有关。
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