14α-tert-butyldimethylsilyloxy-andrographolide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 14α-tert-butyldimethylsilyloxy-andrographolide
• 英文别名: 14-O-tert-butyldimethylsilyl-andrographolide；14-tert-butyldimethylsilylandrographolide；(3E,4S)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethylidene]-4-[tert-butyl(dimethyl)silyl]oxyoxolan-2-one
• 化学式: C₂₆H₄₄O₅Si
• 分子量: 464.718
• InChiKey: QEKAKJCLAFAJTF-GRPWRLQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.99
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  14α-tert-butyldimethylsilyloxy-andrographolide 在 咪唑 、 2-碘酰基苯甲酸 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-oxo-14α,19-di-tert-butyldimethylsilyloxy-andrographolide
  参考文献：
  名称：

  带有α,β-不饱和酮部分的新型穿心莲内酯衍生物的设计、合成和抗癌评价

  摘要：

  设计、合成了一系列基于两个迈克尔受体的 1,2-didehydro-3-ox-andrographolide 衍生物，并评估了它们对两种人类癌细胞系（HCT116 和 MCF-7）的抗癌活性。所有测试化合物均对 HCT116 表现出显着的生长抑制作用，对 MCF-7 细胞增殖具有中等至良好的抑制作用。化合物10b对 HCT116 和 MCF-7 细胞系均显示出最佳抑制活性，IC 50值分别为 2.49 和 7.80 μM。使用流式细胞术对化合物10b对HCT116的细胞周期阻滞和细胞凋亡进行了初步抗癌机制研究，结果表明10b通过以浓度依赖性方式诱导细胞凋亡并在 G 2 /M 期阻滞细胞周期，阻断 HCT116 细胞的增殖。

  DOI：

  10.1016/j.bioorg.2021.104941
• 作为产物：
  描述：

  穿心莲内酯 在 咪唑 、 水 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 16.5h， 生成 14α-tert-butyldimethylsilyloxy-andrographolide
  参考文献：
  名称：

  带有α,β-不饱和酮部分的新型穿心莲内酯衍生物的设计、合成和抗癌评价

  摘要：

  设计、合成了一系列基于两个迈克尔受体的 1,2-didehydro-3-ox-andrographolide 衍生物，并评估了它们对两种人类癌细胞系（HCT116 和 MCF-7）的抗癌活性。所有测试化合物均对 HCT116 表现出显着的生长抑制作用，对 MCF-7 细胞增殖具有中等至良好的抑制作用。化合物10b对 HCT116 和 MCF-7 细胞系均显示出最佳抑制活性，IC 50值分别为 2.49 和 7.80 μM。使用流式细胞术对化合物10b对HCT116的细胞周期阻滞和细胞凋亡进行了初步抗癌机制研究，结果表明10b通过以浓度依赖性方式诱导细胞凋亡并在 G 2 /M 期阻滞细胞周期，阻断 HCT116 细胞的增殖。

  DOI：

  10.1016/j.bioorg.2021.104941

文献信息

• SAR studies of 3,14,19-derivatives of andrographolide on anti-proliferative activity to cancer cells and toxicity to zebrafish: an in vitro and in vivo study
  作者：Yuran Peng、Jingjing Li、Yicheng Sun、Judy Yuet-Wa Chan、Dekuan Sheng、Kun Wang、Ping Wei、Pingkai Ouyang、Decai Wang、Simon Ming Yuen Lee、Guo-Chun Zhou

  DOI：10.1039/c5ra00090d

  日期：——

  Andrographolide is bestowed with an interesting pharmacophore and has attracted numerous studies on the design and synthesis of andrographolide derivatives.

  安龙草素具有有趣的药效团，并吸引了许多研究对安龙草素衍生物的设计和合成进行研究。
• Synthesis and anticancer activity of some novel indolo[3,2-b]andrographolide derivatives as apoptosis-inducing agents
  作者：Yaping Song、Zhengyuan Xin、Yumeng Wan、Jiabin Li、Boping Ye、Xiaowen Xue

  DOI：10.1016/j.ejmech.2014.12.017

  日期：2015.1

  A series of novel indolo[3,2-b]andrographolide derivatives were designed, synthesized and screened in vitro against three human cancer cell lines MCF7 (human breast cancer), HCI'116 (human colon cancer), and DU145 (human prostate cancer). Fourteen compounds 6b, 6e, 6i, 6j, 6l, 6m, 6n, 12a, 12b, 13a, 13b, 15a, 17a, and 17b exhibited better anti-cancer activities than andrographolide for all three human cancer lines, with compound 6l displaying best activity with IC50 values of 1.85, 1.22 and 1.24 mu M against MCF7, HCT116 and DU145 respectively. Preliminary anti-cancer mechanistic investigation was performed in terms of the cell cycle arrest and cell apoptosis assays of compound 6l against HCT116 using flow cytometry, and the results suggested that compound 6l inhibited tumor proliferation through inducing early and late cellular apoptosis in a concentration-dependent manner and causing cell cycle arrest in the S-phase. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice
  作者：Shao-Ru Chen、Feng Li、Mo-Yu Ding、Decai Wang、Qi Zhao、Yitao Wang、Guo-Chun Zhou、Ying Wang

  DOI：10.1016/j.bmc.2018.09.002

  日期：2018.10

  Sustained activation of the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway contributed to the progression of cancer and liver diseases. STAT3 signaling inhibitor has been extensively investigated for pharmacological use. We synthesized a series of andrographolide derivatives, and characterized their activity against STAT3 signaling pathway both in vitro and in the CCl4-induced acute liver damage mice model. Among these derivatives, compound 24 effectively inhibited phosphorylation and dimerization of STAT3 but not its DNA binding activity. Compound 24 significantly ameliorated carbon tetrachloride-induced acute liver damage in vivo without changing mice body weight. Treatment with 24 attenuated hepatic pathologic damage and promoted hepatic proliferation and activation of STAT3. Compound 24 inhibited elevated expression of alpha-smooth muscle actin and serum pro-inflammatory cytokines downstream of STAT3 but not those factors that are regulated by NF-kappa B or SMADs. In summary, our results suggest that compound 24 may serve as a potential therapeutic agent for the treatment of hepatic damage or a liver protection agent via regulating STAT3 activation.
• Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety
  作者：Wei Cai、Jieyi Li、Cheng Chen、Jiajia Wu、Jiabin Li、Xiaowen Xue

  DOI：10.1016/j.bioorg.2021.104941

  日期：2021.7

  A series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory

  设计、合成了一系列基于两个迈克尔受体的 1,2-didehydro-3-ox-andrographolide 衍生物，并评估了它们对两种人类癌细胞系（HCT116 和 MCF-7）的抗癌活性。所有测试化合物均对 HCT116 表现出显着的生长抑制作用，对 MCF-7 细胞增殖具有中等至良好的抑制作用。化合物10b对 HCT116 和 MCF-7 细胞系均显示出最佳抑制活性，IC 50值分别为 2.49 和 7.80 μM。使用流式细胞术对化合物10b对HCT116的细胞周期阻滞和细胞凋亡进行了初步抗癌机制研究，结果表明10b通过以浓度依赖性方式诱导细胞凋亡并在 G 2 /M 期阻滞细胞周期，阻断 HCT116 细胞的增殖。