4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione | 1147123-70-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione
• 英文别名: 4,11-bis(2-aminoethylamino)naphtho[2,3-f][1]benzothiole-5,10-dione
• CAS: 1147123-70-3
• 化学式: C₂₀H₂₀N₄O₂S
• 分子量: 380.47
• InChiKey: UFTNKKBUZZUMBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 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：

  4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione 、 2-氯-1-乙氧基乙胺 在 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 以45%的产率得到4,11-bis[2-(chloroacetamidine)ethylamino]anthra-[2,3-b]thiophene-5,10-dione dihydrochloride
  参考文献：
  名称：

  双（氯乙脒）衍生的杂芳烃融合蒽醌与 tNOX 结合并引起蛋白酶体降解，导致口腔癌细胞中的 c-Flip 下调和凋亡。

  摘要：

  基于蒽醌的嵌入化合物，即阿霉素和米托蒽醌，基于它们结合 DNA 和诱导 DNA 损伤的能力，已在临床上使用。然而，它们的应用受到副作用和耐药性的限制。已经化学合成了与不同杂环稠合的新一代蒽醌衍生物，并筛选了更高的抗癌效力。在我们之前的研究中报道的化合物中，发现 4,11-双（2-（2-氯乙脒）乙基氨基）蒽[2,3-b]噻吩-5,10-二酮二盐酸盐（命名为 2c）具有凋亡作用，但是导致细胞毒性的直接细胞靶点仍然未知。在这里，我们报告了另外两种衍生物 4,11-bis(2-(2-chloroacetamidine)ethylamino)naphtho[2,3-f]indole-5,10-dione dihydrochloride (2a) 和 4 , 11-双(2-(2-氯乙脒)乙基氨基)-2-甲基蒽[2,3-b]呋喃-5,10-二酮二盐酸盐(2b)。我们试图使用分子对接模拟和细胞热位移分析 (CETSA)

  DOI：

  10.3390/cancers14194719
• 作为产物：
  描述：

  4,11-dimethoxyanthra[2,3-b]thiophene-5,10-dione 、 乙二胺 以65%的产率得到4,11-bis(2-aminoethylamino)anthra[2,3-b]thiophene-5,10-dione
  参考文献：
  名称：

  Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones

  摘要：

  We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b] thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b] thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53 (-/-) cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b] thiophene-5,10-dione derivatives. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.047

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.
• Synthesis and cytotoxic properties of 4,11-bis[(aminoethyl)amino]anthra[2,3-b]thiophene-5,10-diones, novel analogues of antitumor anthracene-9,10-diones
  作者：Andrey E. Shchekotikhin、Valeria A. Glazunova、Lyubov G. Dezhenkova、Yuri N. Luzikov、Yuri B. Sinkevich、Leonid V. Kovalenko、Vladimir N. Buyanov、Jan Balzarini、Fong-Chun Huang、Jing-Jer Lin、Hsu-Shan Huang、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.bmc.2009.01.047

  日期：2009.3

  We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b] thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b] thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53 (-/-) cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b] thiophene-5,10-dione derivatives. (C) 2009 Elsevier Ltd. All rights reserved.
• Bis(chloroacetamidino)-Derived Heteroarene-Fused Anthraquinones Bind to and Cause Proteasomal Degradation of tNOX, Leading to c-Flip Downregulation and Apoptosis in Oral Cancer Cells
  作者：Jeng Shiun Chang、Chien-Yu Chen、Alexander S. Tikhomirov、Atikul Islam、Ru-Hao Liang、Chia-Wei Weng、Wei-Hou Wu、Andrey E. Shchekotikhin、Pin Ju Chueh

  DOI：10.3390/cancers14194719

  日期：——

  Anthraquinone-based intercalating compounds, namely doxorubicin and mitoxantrone, have been used clinically based on their capacity to bind DNA and induce DNA damage. However, their applications have been limited by side effects and drug resistance. New-generation anthraquinone derivatives fused with different heterocycles have been chemically synthesized and screened for higher anticancer potency. Among the

  基于蒽醌的嵌入化合物，即阿霉素和米托蒽醌，基于它们结合 DNA 和诱导 DNA 损伤的能力，已在临床上使用。然而，它们的应用受到副作用和耐药性的限制。已经化学合成了与不同杂环稠合的新一代蒽醌衍生物，并筛选了更高的抗癌效力。在我们之前的研究中报道的化合物中，发现 4,11-双（2-（2-氯乙脒）乙基氨基）蒽[2,3-b]噻吩-5,10-二酮二盐酸盐（命名为 2c）具有凋亡作用，但是导致细胞毒性的直接细胞靶点仍然未知。在这里，我们报告了另外两种衍生物 4,11-bis(2-(2-chloroacetamidine)ethylamino)naphtho[2,3-f]indole-5,10-dione dihydrochloride (2a) 和 4 , 11-双(2-(2-氯乙脒)乙基氨基)-2-甲基蒽[2,3-b]呋喃-5,10-二酮二盐酸盐(2b)。我们试图使用分子对接模拟和细胞热位移分析 (CETSA)