State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
Molecules. 2013 Nov 13;18(11):13992-4012. doi: 10.3390/molecules181113992.
A series of 4β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC₅₀ values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue.
设计并合成了一系列通过点击化学方法连接的 4β-三唑葡萄糖鬼臼毒素缀合物。采用 MTT 法评价了所有化合物对五种人癌细胞系（HL-60、SMMC-7721、A-549、MCF-7、SW480）的抗癌活性。这些三唑衍生物大多数具有良好的抗癌活性。其中，化合物 35 对所有五种测试的癌细胞系表现出最高的活性，IC50 值范围为 0.59 至 2.90 μM，比目前临床使用的药物依托泊苷活性更强。构效关系分析表明，葡萄糖残基上的酰基取代、聚乙二醇接头的长度和鬼臼毒素支架的 4′-去甲基化都能显著影响抗癌活性的强度。值得注意的是，带有戊酰基葡萄糖残基的衍生物比带有游离葡萄糖或乙酰化葡萄糖残基的类似物具有更高的活性。
