3-(4-methoxy-2-nitro-phenylamino)-2,2-dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione | 1201786-16-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 3-(4-methoxy-2-nitro-phenylamino)-2,2-dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione
• 英文别名: 3-(4-methoxy-2-nitroanilino)-2,2-dimethyl-3H-benzo[g][1]benzofuran-4,5-dione
• CAS: 1201786-16-4
• 化学式: C₂₁H₁₈N₂O₆
• 分子量: 394.384
• InChiKey: BREQNUBZQXSUPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  黄钟花醌 在 溴 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 生成 3-(4-methoxy-2-nitro-phenylamino)-2,2-dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair

  摘要：

  The current study describes that nor-beta-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-beta-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-beta-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.

  DOI：

  10.1590/s0103-50532013000100019

文献信息

• [EN] LAPACHONE DERIVATIVES CONTAINING TWO REDOX CENTERS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS DE LAPACHONE CONTENANT DEUX CENTRES REDOX ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：UNIV TEXAS

  公开号：WO2017070012A1

  公开（公告）日：2017-04-27

  Provided herein are compounds containing two redox centers including a chalcogen redox center of the formula: wherein: R1, R2, X1, X2, Y1, and m are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.

  本文提供了含有两个氧化还原中心的化合物，其中包括一个硫属氧化还原中心，其化学式如下：其中：R1、R2、X1、X2、Y1和m如本文所定义。本文还提供了所述化合物的药物组合物以及使用这些化合物进行治疗的方法，包括它们在癌症治疗中的应用。
• 3-Arylamino and 3-Alkoxy-nor-β-lapachone Derivatives: Synthesis and Cytotoxicity against Cancer Cell Lines
  作者：Eufrânio N. da Silva Júnior、Clara F. de Deus、Bruno C. Cavalcanti、Cláudia Pessoa、Letícia V. Costa-Lotufo、Raquel C. Montenegro、Manoel O. de Moraes、Maria do Carmo F. R. Pinto、Carlos A. de Simone、Vitor F. Ferreira、Marilia O. F. Goulart、Carlos Kleber Z. Andrade、Antônio V. Pinto

  DOI：10.1021/jm900865m

  日期：2010.1.14

  Several 3-arylamino and 3-alkoxy-nor-β-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC50 below 2 μM. The arylamino para-nitro and the 2,4-dimethoxy substituted naphthoquinones showed the best cytoxicity profile, while the ortho-nitro and

  以中等至高产率合成了几种 3-芳基氨基和 3-烷氧基-去甲-β-拉帕酮衍生物，发现对癌细胞 SF295（中枢神经系统）、HCT8（结肠）、MDA-MB435（黑色素瘤）、和 HL60（白血病），IC 50低于 2 μM。芳氨基对硝基和 2,4-二甲氧基取代的萘醌表现出最好的细胞毒性，而邻硝基和 2,4-二甲氧基取代的萘醌比多柔比星更具选择性，并且与前体拉帕酮相似，因此很有前景。抗癌药物开发中的新先导化合物。
• The evaluation of quinonoid compounds against Trypanosoma cruzi: Synthesis of imidazolic anthraquinones, nor-β-lapachone derivatives and β-lapachone-based 1,2,3-triazoles
  作者：Eufrânio N. da Silva Júnior、Tiago T. Guimarães、Rubem F.S. Menna-Barreto、Maria do Carmo F.R. Pinto、Carlos A. de Simone、Claudia Pessoa、Bruno C. Cavalcanti、José R. Sabino、Carlos Kleber Z. Andrade、Marilia O.F. Goulart、Solange L. de Castro、Antônio V. Pinto

  DOI：10.1016/j.bmc.2010.03.029

  日期：2010.5

  In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream trypomastigote forms of the parasite. Compounds 2,2-dimethyl-3-(2,4-dibromophenylamino)-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione, IC50/24 h 24.9 +/- 7.4 and 4-azido-3-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione with 23.4 +/- 3.8 mu M showed a trypanosomicidal activity higher than benznidazole. These results demonstrate the potential of naphthoquinone derivatives as novel structures for the development of alternative drugs for Chagas' disease. (c) 2010 Elsevier Ltd. All rights reserved.
• Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair
  作者：Bruno C. Cavalcanti、Igor O. Cabral、Felipe A. R. Rodrigues、Francisco W. A. Barros、Danilo D. Rocha、Hemerson I. F. Magalhães、Dinara J. Moura、Jenifer Saffi、João A. P. Henriques、Tatiane S. C. Carvalho、Manoel O. Moraes、Cláudia Pessoa、Isadora M. M. de Melo、Eufrânio N. da Silva Júnior

  DOI：10.1590/s0103-50532013000100019

  日期：——

  The current study describes that nor-beta-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-beta-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-beta-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.