Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin
Synthesis and anticancer activities of fatty acid analogs of podophyllotoxin
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DOI：
10.1007/s11745-004-1215-5
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发表时间：
2004-02-01
期刊：
影响因子：
1.9
通讯作者：
Khan, IA
中科院分区：
文献类型：
--
作者：
Mustafa, J;Khan, SI;Khan, IA
鬼臼毒素的衍生物是通过将 10 FA 与鬼臼毒素的 C-4-α-羟基官能团偶联来制备的。 FA和鬼臼毒素之间的偶联反应是通过二环己基碳二亚胺在催化量的二甲氨基吡啶存在下进行的，以定量产率产生所需产物。掺入的 FA 如下：10-羟基癸酸、12-羟基十二烷酸、15-羟基十五烷酸、16-羟基十六烷酸、12-羟基十八烷-Z-9-烯酸、二十碳五烯酸-Z-5,8,11,14-四烯酸、二十碳五烯酸-Z-8,1 1, 14-三烯酸、 eicosa-Z-11,14-二烯酸、eicosa-Z-11-烯酸和二十烷酸。光谱研究证实了所需产物的形成。研究了新分子对一组人类癌细胞系（包括 SK-MEL、KB、BT-549、SK-OV-3（实体瘤）和 HL-60（人类白血病）细胞）的体外抗癌活性。大多数类似物对癌细胞具有细胞毒性，而对正常细胞没有观察到任何作用，这与母体化合物鬼臼毒素不同，其使用由于其严重的副作用而受到限制。
Derivatives of podophyllotoxin were prepared by coupling 10 FA with the C-4-alpha-hydroxy function of podophyllotoxin. The coupling reactions between FA and podophyllotoxin were carried out by dicyclohexylcarbodiimide in the presence of a catalytic amount of climethylaminopyridine to produce quantitative yields of desired products. FA incorporated were the following: 10-hydroxydecanoic, 12-hydroxydodecanoic, 15-hydroxypentadecanoic, 16-hydroxyhexadecanoic, 12-hydroxyoctadec-Z-9-enoic, eicosa-Z-5,8,11,14-tetraenoic, eicosa-Z-8,1 1, 14-trienoic, eicosa-Z-11,14-dienoic, eicosa-Z-11-enoic, and eicosanoic acids. Spectroscopic studies confirmed the formation of the desired products. New molecules were investigated for their in vitro anticancer activity against a panel of human cancer cell lines including SK-MEL, KB, BT-549, SK-OV-3 (solid tumors), and HL-60 (human leukemia) cells. Most of the analogs were cytotoxic against cancerous cells, whereas no effect was observed against normal cells, unlike the parent compound poclophyllotoxin, the use of which is limited due to its severe side effects.