3-bromo-4-azide-β-lapachone

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 3-bromo-4-azide-β-lapachone
• 英文别名: 4-azido-3-bromo-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione；(3R,4S)-4-azido-3-bromo-2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione
• 化学式: C₁₅H₁₂BrN₃O₃
• 分子量: 362.183
• InChiKey: SEEHGZFDYGBTEN-IINYFYTJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-bromo-4-azide-β-lapachone 在 copper(ll) sulfate pentahydrate 、 sodium acetate 、 溶剂黄146 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 2-bromo-1-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-3,3-dimethyl-2,3-dihydro-1H-benzo[a]pyrano[2,3-c]phenazine
  参考文献：
  名称：

  On the Search for Potential Antimycobacterial Drugs: Synthesis of Naphthoquinoidal, Phenazinic and 1,2,3-Triazolic Compounds and Evaluation AgainstMycobacterium tuberculosis

  摘要：

  Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values <= 6.25 mu g mL(-1). These substances are promising antimycobacterial prototypes.

  DOI：

  10.5935/0103-5053.20150067
• 作为产物：
  描述：

  3,4-二氢-2,2-二甲基-2H-萘并[1,2-B]吡喃-5,6-二酮 在 sodium azide 、 溴 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 生成 3-bromo-4-azide-β-lapachone
  参考文献：
  名称：

  Molecular hybridization as a powerful tool towards multitarget quinoidal systems: synthesis, trypanocidal and antitumor activities of naphthoquinone-based 5-iodo-1,4-disubstituted-, 1,4- and 1,5-disubstituted-1,2,3-triazoles

  摘要：

  一些混合化合物展示出有希望的钩端螺旋体杀灭和抗癌活性。

  DOI：

  10.1039/c6md00216a

文献信息

• Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights
  作者：Eduardo H.G. da Cruz、Molly A. Silvers、Guilherme A.M. Jardim、Jarbas M. Resende、Bruno C. Cavalcanti、Igor S. Bomfim、Claudia Pessoa、Carlos A. de Simone、Giancarlo V. Botteselle、Antonio L. Braga、Divya K. Nair、Irishi N.N. Namboothiri、David A. Boothman、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.ejmech.2016.06.019

  日期：2016.10

  Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian

  使用点击化学（铜催化叠氮化物-炔烃 1,3-偶极环加成）合成含硒醌基 1,2,3-三唑，并针对六种类型的癌细胞系进行评估：HL-60（人早幼粒细胞白血病细胞） ）、HCT-116（人结肠癌细胞）、PC3（人前列腺细胞）、SF295（人胶质母细胞瘤细胞）、MDA-MB-435（黑色素瘤细胞）和OVCAR-8（人卵巢癌细胞）。一些化合物显示 IC 50值 < 0.3 μM。还使用非肿瘤细胞（例如外周血单核（PBMC）、V79 和 L929 细胞）测定了所评估的醌的细胞毒性潜力。NAD(P)H:醌氧化还原酶 1 (NQO1) 的机制作用也得到了阐明。这些化合物可以为更有效的抗癌药物开发和递送提供有前途的新先导衍生物，并且代表了报道的最活跃的拉帕酮类之一。
• It takes two to tango: synthesis of cytotoxic quinones containing two redox active centers with potential antitumor activity
  作者：Daisy J. B. Lima、Renata G. Almeida、Guilherme A. M. Jardim、Breno P. A. Barbosa、Augusto C. C. Santos、Wagner O. Valença、Marcos R. Scheide、Claudia C. Gatto、Guilherme G. C. de Carvalho、Pedro M. S. Costa、Claudia Pessoa、Cynthia L. M. Pereira、Claus Jacob、Antonio L. Braga、Eufrânio N. da Silva Júnior

  DOI：10.1039/d1md00168j

  日期：——

  We report the synthesis of 47 new quinone-based derivatives via click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These compounds combine two redox centers, such as an ortho-quinone/para-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC50 values below 0.5 μM in cancer cell lines

  我们报告了通过点击化学合成 47 种新的基于醌的衍生物及其随后对癌细胞系和对照 L929 鼠成纤维细胞系的评估。这些化合物结合了两个氧化还原中心，例如邻-醌/对-醌或醌/硒与 1,2,3-三唑核。其中几种化合物在癌细胞系中的IC 50值低于 0.5 μM，在对照细胞系 L929 中的细胞毒性显着降低，选择性指数良好。因此，我们的研究证实了使用完整且非常多样化的醌类化合物，这些化合物具有针对某些癌细胞系的潜在应用。
• Synthesis of Selenium-Quinone Hybrid Compounds with Potential Antitumor Activity via Rh-Catalyzed C-H Bond Activation and Click Reactions
  作者：Guilherme Jardim、Daisy Lima、Wagner Valença、Daisy Lima、Bruno Cavalcanti、Claudia Pessoa、Jamal Rafique、Antonio Braga、Claus Jacob、Eufrânio da Silva Júnior、Eduardo da Cruz

  DOI：10.3390/molecules23010083

  日期：——

  were synthesized using rhodium-catalyzed C-H bond activation and click reactions. All compounds were evaluated against five types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), SF295 (human glioblastoma cells), NCIH-460 (human lung cells) and PC3 (human prostate cancer cells). Some compounds showed good activity with IC50 values below 1 µM.

  为了继续探索新的氧化还原调节催化抗肿瘤分子，使用铑催化的 CH 键活化和点击反应合成了含硒醌基 1,2,3-三唑。所有化合物都针对五种类型的癌细胞系进行了评估：HL-60（人早幼粒细胞白血病细胞）、HCT-116（人结肠癌细胞）、SF295（人胶质母细胞瘤细胞）、NCIH-460（人肺细胞）和 PC3（人前列腺癌细胞）。一些化合物显示出良好的活性，IC50 值低于 1 µM。萘醌衍生物的细胞毒性潜力也在非肿瘤细胞中进行了评估，例如 L929 细胞。总体而言，这些化合物代表了有前途的新先导衍生物，代表了一类具有潜在抗肿瘤活性的新型含硫衍生物。
• 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.
• Synthesis and evaluation of quinonoid compounds against tumor cell lines
  作者：Eufrânio N. da Silva、Bruno C. Cavalcanti、Tiago T. Guimarães、Maria do Carmo F.R. Pinto、Igor O. Cabral、Cláudia Pessoa、Letícia V. Costa-Lotufo、Manoel O. de Moraes、Carlos K.Z. de Andrade、Marcelo R. dos Santos、Carlos A. de Simone、Marilia O.F. Goulart、Antonio V. Pinto

  DOI：10.1016/j.ejmech.2010.11.006

  日期：2011.1

  Thirty two compounds were synthesized in moderate to high yields and showed activity against cancer cells HL-60 (leukemia), MDA-MB435 (melanoma), HCT-8 (colon) and SF295 (central nervous system), with IC50 below 2 mu M for some compounds. The beta-lapachone-based 1,2,3-triazoles showed the best cytoxicity profile and emerge as promising anticancer prototypes. Insights about the reactive oxygen species (ROS) mechanism of anticancer action for some compounds were obtained by addition of 1-bromoheptane that deplete reduced glutathione (GSH) content and by using N-acetylcysteine that protects cells against apoptotic cellular death, as well by analysis of thiobarbituric acid reactive substances (TBARS) formation, and oxidative DNA damage after treatment detected by the comet assay with the bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (ENDOIII). (C) 2010 Elsevier Masson SAS. All rights reserved.