(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(3-phenoxyphenyl)acetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(3-phenoxyphenyl)acetate
• 英文别名: [(1R)-1-(5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl] 2-(3-phenoxyphenyl)acetate
• 化学式: C₃₀H₂₆O₇
• 分子量: 498.532
• InChiKey: MQEAKUQVTOFJSV-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  紫草素 、 3-苯氧基苯乙酸 在 N,N'-二环己基碳二亚胺 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 14.58h， 以57%的产率得到(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(3-phenoxyphenyl)acetate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel shikonin ester derivatives as potential anti-cancer agents

  摘要：

  紫草素此前曾被报道为一种有效的抗癌药物，可通过多种途径诱导细胞凋亡。为了优化其促凋亡功能的有效性，紫草素被选为获得紫草素酯衍生物（3a-3n）的最佳化合物，因为它在侧链羟基位置上具有酯基团，并且生物活性被评估为有效的许多癌细胞系的抗增殖抑制剂。其中化合物3j对人肝癌细胞系(HepG2)表现出更好的抗癌活性，IC50值为0.759 μM，优于紫草素的1.288 μM。流式细胞术结果显示，化合物3j抑制细胞生长，使细胞周期停滞在G2/M期。同时，Annexin V联合碘化丙啶检测观察到3j明显诱导细胞凋亡，表明3j以剂量和时间依赖性方式诱导HepG2细胞凋亡。为了探讨3j诱导细胞凋亡过程中的潜在机制，采用蛋白质印迹技术，观察到caspase-9的裂解，但未观察到caspase-8的裂解。此外，p53蛋白表达的升高与Bcl-2蛋白水平的降低以及Bax蛋白和细胞色素C水平的升高呈正相关。这就说明细胞凋亡过程中 p53 指导的线粒体凋亡途径受到 3j 的诱导。基于这些数据，我们得出结论，在 14 种新合成的化合物中，化合物 3j 具有最好的抗增殖和促凋亡作用，并且它可能是癌症治疗的有效候选者。

  DOI：

  10.1039/c4ra05610h

文献信息

• Synthesis and biological evaluation of novel shikonin ester derivatives as potential anti-cancer agents
  作者：Shahla Karim Baloch†、Li-Jun Ling†、Han-Yue Qiu、Lin Ma、Hong-Yan Lin、Shou-Cheng Huang、Jin-Liang Qi、Xiao-Ming Wang、Gui-Hua Lu、Yong-Hua Yang

  DOI：10.1039/c4ra05610h

  日期：——

  Shikonin has previously been reported to function as a potent anti-cancer drug that induces cell apoptosis via diverse pathways. To optimize the effectiveness of its pro-apoptotic functions, shikonin was chosen as the best compound for obtaining shikonin ester derivatives (3a–3n) because it possesses an ester group on the side chain hydroxyl position, and the biological activity was evaluated as a potent anti-proliferating inhibitor for many cancer cell lines. Among these compounds, compound 3j exhibited better anti-cancer activities against human hepatocellular carcinoma cell line (HepG2) with an IC50 value of 0.759 μM which was better than that of shikonin which was 1.288 μM. The flow cytometry results showed that compound 3j inhibited the cell growth and caused the cell cycle to be arrested at the G2/M phase. Meanwhile, obvious apoptosis induced by 3j was observed using the Annexin V combined with propidium iodide assay, showing that 3j induced apoptosis of HepG2 cells in a dose and time dependent manner. To investigate the underlying mechanism in the process of apoptosis induced by 3j, the western blot technique was used and the cleavage of caspase-9 was observed but not that of caspase-8. Furthermore, the elevated expression of the p53 protein was positively correlated with the decreased Bcl-2 protein levels and increased Bax protein and the cytochrome C levels. This indicated that the mitochondrial apoptosis pathway directed by p53 responded in the process of apoptosis was induced by 3j. Based on these data, we conclude that compound 3j has the best anti-proliferating and pro-apoptotic effect among the 14 newly synthesized compounds, and it could be a potent candidate for cancer therapy.

  紫草素此前曾被报道为一种有效的抗癌药物，可通过多种途径诱导细胞凋亡。为了优化其促凋亡功能的有效性，紫草素被选为获得紫草素酯衍生物（3a-3n）的最佳化合物，因为它在侧链羟基位置上具有酯基团，并且生物活性被评估为有效的许多癌细胞系的抗增殖抑制剂。其中化合物3j对人肝癌细胞系(HepG2)表现出更好的抗癌活性，IC50值为0.759 μM，优于紫草素的1.288 μM。流式细胞术结果显示，化合物3j抑制细胞生长，使细胞周期停滞在G2/M期。同时，Annexin V联合碘化丙啶检测观察到3j明显诱导细胞凋亡，表明3j以剂量和时间依赖性方式诱导HepG2细胞凋亡。为了探讨3j诱导细胞凋亡过程中的潜在机制，采用蛋白质印迹技术，观察到caspase-9的裂解，但未观察到caspase-8的裂解。此外，p53蛋白表达的升高与Bcl-2蛋白水平的降低以及Bax蛋白和细胞色素C水平的升高呈正相关。这就说明细胞凋亡过程中 p53 指导的线粒体凋亡途径受到 3j 的诱导。基于这些数据，我们得出结论，在 14 种新合成的化合物中，化合物 3j 具有最好的抗增殖和促凋亡作用，并且它可能是癌症治疗的有效候选者。