Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic effects on human cancer cells
Synthesis of solasodine glycoside derivatives and evaluation of their cytotoxic effects on human cancer cells
复制标题
茄碱糖苷衍生物的合成及其对人癌细胞的细胞毒作用评价
DOI：
10.5582/ddt.2012.v6.1.9
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Lou, Hongxiang
中科院分区：
文献类型：
--
作者：
Cui, Changzhi;Wen, Xuesen;Lou, Hongxiang
茄次碱苷类化合物，如茄边碱，已被证明是非常重要的抗癌剂。为了发现更有效的细胞毒药物并探索初步的构效关系，通过转糖基化策略合成了一系列新的澳洲茄定苷2-9，并通过MTT法评价了它们对一组人癌细胞系（MCF-7、KB、K562和PC 3细胞）的细胞毒活性。结果表明，化合物2、8和9分别以鼠李糖、2-羟基乙氧基甲基和1，3-二羟基丙氧基甲基为取代基，具有较强的抗癌活性。潜在的机制测试表明，这些化合物可以通过DAPI染色以及Annexin V和碘化丙啶结合检测到的诱导凋亡。细胞周期分析表明，当暴露于这些化合物通过流式细胞术检查时，癌细胞主要被阻滞在G2/M期。这些化合物可作为开发用于癌症治疗的新型化学治疗剂的主要候选物。
Solasodine glycosides, such as solamargine, have been proved to be very important anti-cancer agents. In order to discover more potent cytotoxic agents and explore the preliminary structure activity relationship, a new series of solasodine glycosides 2-9 were synthesized via a transglycosylation strategy, and their cytotoxic activity against a panel of human cancer cell lines (MCF-7, KB, K562, and PC3 cells) were evaluated by MTT assays. The results indicated that compounds 2, 8, and 9 with the substitute moiety of rhamnose, 2-hydroxyethoxymethyl, and 1,3-dihydroxypropan2-yloxy-methyl, respectively, exhibited quite strong anticancer activity. The underlying mechanism tests demonstrated that these compounds could induce apoptosis detected by DAPI staining, and Annexin V and propidium iodide binding. Cell cycle analysis indicated that the cancer cells were predominantly arrested at the G2/M phase when exposure to these compounds was examined by flow cytometry. These compounds may serve as lead candidates in the development of novel chemotherapeutics for cancer treatment.