3-((dimethylamino)methyl)-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione | 423757-25-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 3-((dimethylamino)methyl)-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
• 英文别名: 3-N,N-dimethylaminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione；3-[(dimethylamino)methyl]-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
• CAS: 423757-25-9
• 化学式: C₁₉H₁₆N₂O₄
• 分子量: 336.347
• InChiKey: UPDRUKMTENLOFS-UHFFFAOYSA-N

物化性质

• 沸点：
  589.0±45.0 °C(Predicted)
• 密度：
  1.495±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  93.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-((dimethylamino)methyl)-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione 以 四氢呋喃 、 氯仿 为溶剂， 反应 0.33h， 生成 3-[(2-Amino-ethylamino)-methyl]-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
  参考文献：
  名称：

  3-Aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione for circumvention of anticancer drug resistance

  摘要：

  A series of 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3 -f]indole-5,10-dione was synthesized by Mannich reaction or by the transamination of 3-dimethylaminomethyl 4,11-dihydroxy- or 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione. The potency of novel derivatives was tested on a National Cancer Institute panel of 60 human tumor cell lines as well as in cells with genetically defined determinants of cytotoxic drug resistance, P-glycoprotein (Pgp) expression, and p53 inactivation. Mannich derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione with an additional amino function in their side chain, demonstrated equal cytotoxicity against the parental K562 leukemia cells and their Pgp-positive subline, whereas the latter showed similar to 7-fold resistance to adriamycin, a Pgp transported drug. 3-(1-Piperazinyl)methyl and 3-(quinuclidin-3-yl)aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione killed HCT116 colon carcinoma cells (carrying wild type p53) and their p53-null variant within the similar range of concentrations. We conclude that Mannich modification of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione, especially when cyclic diamine (e.g., piperazine, quinuclidine) is used, confers an important feature to the resulting compounds, namely, the potency for tumor cells otherwise resistant to a variety of anticancer drugs. (c) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.044
• 作为产物：
  描述：

  3-N,N-dimethylaminomethyl-4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione 在 盐酸 、 溶剂黄146 作用下， 以 水 为溶剂， 生成 3-((dimethylamino)methyl)-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
  参考文献：
  名称：

  Synthesis and evaluation of new antitumor 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones

  摘要：

  A series of new 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones 6-13 bearing the cyclic diamine in the position 3 of the indole ring was synthesized. The majority of new compounds demonstrated a superior cytotoxicity than doxorubicin against a panel of mammalian tumor cells with determinants of altered drug response, that is, Pgp expression or p53 inactivation. For naphtho[2,3-f] indole-5,10-diones 6-9 bearing 3-aminopyrrolidine in the side chains, the ability to bind double-stranded DNA and inhibit topoisomerases 1 and 2 mediated relaxation of supercoiled DNA were demonstrated. Only one isomer, (R)-4,11-dihydroxy-3-((pyrrolidin-3-ylamino)methyl)-1H-naphtho[2,3-f]indole-5,10-dione (7) induced the formation of specific DNA cleavage products similar to the known topoisomerase 1 inhibitors camptothecin and indenoisoquinoline MJ-III-65, suggesting a role of the structure of the side chain of 3-aminomethylnaphtho[2,3-f]indole-5,10-diones in interaction with the target. Compound 7 demonstrated an antitumor activity in mice with P388 leukemia transplants whereas its enantiomer 6 was inactive. Thus, 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f] indole-5,10-dione emerge as a new prospective chemotype for the search of antitumor agents. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.021

文献信息

• ——
  作者：A. E. Shchekotikhin、E. P. Baberkina、K. F. Turchin、V. N. Buyanov、N. N. Suvorov

  DOI：10.1023/a:1012727331823

  日期：——
• 3-Aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione for circumvention of anticancer drug resistance
  作者：Andrey E. Shchekotikhin、Alexander A. Shtil、Yuri N. Luzikov、Tatyana V. Bobrysheva、Vladimir N. Buyanov、Maria N. Preobrazhenskaya

  DOI：10.1016/j.bmc.2004.12.044

  日期：2005.3

  A series of 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3 -f]indole-5,10-dione was synthesized by Mannich reaction or by the transamination of 3-dimethylaminomethyl 4,11-dihydroxy- or 4,11-dimethoxynaphtho[2,3-f]indole-5,10-dione. The potency of novel derivatives was tested on a National Cancer Institute panel of 60 human tumor cell lines as well as in cells with genetically defined determinants of cytotoxic drug resistance, P-glycoprotein (Pgp) expression, and p53 inactivation. Mannich derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione with an additional amino function in their side chain, demonstrated equal cytotoxicity against the parental K562 leukemia cells and their Pgp-positive subline, whereas the latter showed similar to 7-fold resistance to adriamycin, a Pgp transported drug. 3-(1-Piperazinyl)methyl and 3-(quinuclidin-3-yl)aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione killed HCT116 colon carcinoma cells (carrying wild type p53) and their p53-null variant within the similar range of concentrations. We conclude that Mannich modification of 4,11-dihydroxynaphtho[2,3-f]indole-5,10-dione, especially when cyclic diamine (e.g., piperazine, quinuclidine) is used, confers an important feature to the resulting compounds, namely, the potency for tumor cells otherwise resistant to a variety of anticancer drugs. (c) 2004 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of new antitumor 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones
  作者：Andrey E. Shchekotikhin、Valeria A. Glazunova、Lyubov G. Dezhenkova、Yuri N. Luzikov、Vladimir N. Buyanov、Helena M. Treshalina、Nina A. Lesnaya、Vladimir I. Romanenko、Dmitry N. Kaluzhny、Jan Balzarini、Keli Agama、Yves Pommier、Alexander A. Shtil、Maria N. Preobrazhenskaya

  DOI：10.1016/j.ejmech.2014.09.021

  日期：2014.10

  A series of new 3-aminomethyl-4,11-dihydroxynaphtho[2,3-f]indole-5,10-diones 6-13 bearing the cyclic diamine in the position 3 of the indole ring was synthesized. The majority of new compounds demonstrated a superior cytotoxicity than doxorubicin against a panel of mammalian tumor cells with determinants of altered drug response, that is, Pgp expression or p53 inactivation. For naphtho[2,3-f] indole-5,10-diones 6-9 bearing 3-aminopyrrolidine in the side chains, the ability to bind double-stranded DNA and inhibit topoisomerases 1 and 2 mediated relaxation of supercoiled DNA were demonstrated. Only one isomer, (R)-4,11-dihydroxy-3-((pyrrolidin-3-ylamino)methyl)-1H-naphtho[2,3-f]indole-5,10-dione (7) induced the formation of specific DNA cleavage products similar to the known topoisomerase 1 inhibitors camptothecin and indenoisoquinoline MJ-III-65, suggesting a role of the structure of the side chain of 3-aminomethylnaphtho[2,3-f]indole-5,10-diones in interaction with the target. Compound 7 demonstrated an antitumor activity in mice with P388 leukemia transplants whereas its enantiomer 6 was inactive. Thus, 3-aminomethyl derivatives of 4,11-dihydroxynaphtho[2,3-f] indole-5,10-dione emerge as a new prospective chemotype for the search of antitumor agents. (C) 2014 Elsevier Masson SAS. All rights reserved.