4-[(2-aminoethyl)amino]-11-[(3-aminopropyl)amino]anthra[2,3-b]thiophene-5,10-dione | 1427764-34-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 4-[(2-aminoethyl)amino]-11-[(3-aminopropyl)amino]anthra[2,3-b]thiophene-5,10-dione
• 英文别名: 4-(2-Aminoethylamino)-11-(3-aminopropylamino)naphtho[2,3-f][1]benzothiole-5,10-dione；4-(2-aminoethylamino)-11-(3-aminopropylamino)naphtho[2,3-f][1]benzothiole-5,10-dione
• CAS: 1427764-34-8
• 化学式: C₂₁H₂₂N₄O₂S
• 分子量: 394.497
• InChiKey: QIQUJDHUZVYEIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[(2-aminoethyl)amino]-11-[(3-aminopropyl)amino]anthra[2,3-b]thiophene-5,10-dione 、 2-氯-1-乙氧基乙胺 在 三乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 3.0h， 以41%的产率得到4-[2-(chloroacetamidine)ethylamino]-11-[3-(chloroacetamidine)propylamino]anthra[2,3-b]-thiophene-5,10-dione dihydrochloride
  参考文献：
  名称：

  Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells

  摘要：

  We previously found that two neighboring G-quadruplexes behave as a molecular switch controlling the expression of HRAS (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl Acids Res. 2014,,I)01:: 10.1093/nar/gku574). In this study we have,designed anthrathiophenediones with two chloroacetamidine-containing,side chains (CATDs) as G-quadruplex binders and have examined their anticancer activity in T24 bladder cancer cells bearing mutant I-IRAS and in T24 xenografts. The designed CATD8 (3a-e); bearing alkyl side chains of different length, penetrate T24 cancer cells more than their analogues with guanidine,containing side chains. The lead compounds 3a and 3c inhibit HRAS expression, metabolic activity, and colony formation in T24 cancer cells. They also activate a strong apoptotic response, as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide assays. Apoptosis occurs under conditions where cyclin. D1 is down-regulated and the cell cycle arrested in G2 phase. Finally, compound 3a inhibits the growth of T24 xenografts and increases the median survival time of nude, mice.

  DOI：

  10.1021/acs.jmedchem.5b00409
• 作为产物：
  描述：

  4,11-dibutoxyanthra[2,3-b]thiophene-5,10-dione 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 4-[(2-aminoethyl)amino]-11-[(3-aminopropyl)amino]anthra[2,3-b]thiophene-5,10-dione
  参考文献：
  名称：

  Guanidino Anthrathiophenediones as G-Quadruplex Binders: Uptake, Intracellular Localization, and Anti-Harvey-ras Gene Activity in Bladder Cancer Cells

  摘要：

  We prepared a series of anthrathiophenediones (ATPDs) with guanidino-alkyl side chains of different length (compounds 1, 10-13). The aim was to investigate their interaction with DNA and RNA G-quadruplexes, their uptake in malignant and nonmalignant cells, and their capacity to modulate gene expression and inhibit cell growth. Flow c-ytometry showed that the ATPDs enter more efficiently in malignant T24 bladder cells than in nonmalignant embryonic kidney 293 or fibroblast NIH 3T3 cells. In T24 malignant cells, compound 1, with two ethyl side chains, is taken up by endocytosis, while 12 and 13, with respectively propyl and butyl side chains, are transported by passive diffusion. The designed ATPDs localize in the cytoplasm and nucleus and tightly bind to DNA and RNA G-quadruplexes. They also decrease HRAS expression, increase the cell population in G(0)/(1), and strongly inhibit proliferation in malignant T24 bladder cells, but not in nonmalignant 293 or NIH 3T3 cells.

  DOI：

  10.1021/jm3019063

文献信息

• Guanidino Anthrathiophenediones as G-Quadruplex Binders: Uptake, Intracellular Localization, and Anti-Harvey-ras Gene Activity in Bladder Cancer Cells
  作者：Susanna Cogoi、Andrey E. Shchekotikhin、Alexandro Membrino、Yuri B. Sinkevich、Luigi E. Xodo

  DOI：10.1021/jm3019063

  日期：2013.4.11

  We prepared a series of anthrathiophenediones (ATPDs) with guanidino-alkyl side chains of different length (compounds 1, 10-13). The aim was to investigate their interaction with DNA and RNA G-quadruplexes, their uptake in malignant and nonmalignant cells, and their capacity to modulate gene expression and inhibit cell growth. Flow c-ytometry showed that the ATPDs enter more efficiently in malignant T24 bladder cells than in nonmalignant embryonic kidney 293 or fibroblast NIH 3T3 cells. In T24 malignant cells, compound 1, with two ethyl side chains, is taken up by endocytosis, while 12 and 13, with respectively propyl and butyl side chains, are transported by passive diffusion. The designed ATPDs localize in the cytoplasm and nucleus and tightly bind to DNA and RNA G-quadruplexes. They also decrease HRAS expression, increase the cell population in G(0)/(1), and strongly inhibit proliferation in malignant T24 bladder cells, but not in nonmalignant 293 or NIH 3T3 cells.
• Potent Apoptotic Response Induced by Chloroacetamidine Anthrathiophenediones in Bladder Cancer Cells
  作者：Susanna Cogoi、Sonia Zorzet、Andrey E. Shchekotikhin、Luigi E. Xodo

  DOI：10.1021/acs.jmedchem.5b00409

  日期：2015.7.23

  We previously found that two neighboring G-quadruplexes behave as a molecular switch controlling the expression of HRAS (Cogoi, S.; Schekotikhin, A. E.; Xodo, L. E. Nucl Acids Res. 2014,,I)01:: 10.1093/nar/gku574). In this study we have,designed anthrathiophenediones with two chloroacetamidine-containing,side chains (CATDs) as G-quadruplex binders and have examined their anticancer activity in T24 bladder cancer cells bearing mutant I-IRAS and in T24 xenografts. The designed CATD8 (3a-e); bearing alkyl side chains of different length, penetrate T24 cancer cells more than their analogues with guanidine,containing side chains. The lead compounds 3a and 3c inhibit HRAS expression, metabolic activity, and colony formation in T24 cancer cells. They also activate a strong apoptotic response, as indicated by PARP-1, caspases 3/7, and annexin V/propidium iodide assays. Apoptosis occurs under conditions where cyclin. D1 is down-regulated and the cell cycle arrested in G2 phase. Finally, compound 3a inhibits the growth of T24 xenografts and increases the median survival time of nude, mice.