5,7-dibromo-1-(4-bromomethylbenzyl)-1H-indole-2,3-dione | 1344698-26-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5,7-dibromo-1-(4-bromomethylbenzyl)-1H-indole-2,3-dione
• 英文别名: 5,7-Dibromo-1-[[4-(bromomethyl)phenyl]methyl]indole-2,3-dione
• CAS: 1344698-26-5
• 化学式: C₁₆H₁₀Br₃NO₂
• 分子量: 487.973
• InChiKey: PHSCBUUOHGKUOG-UHFFFAOYSA-N

物化性质

• 沸点：
  565.6±60.0 °C(Predicted)
• 密度：
  2.010±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,7-dibromo-1-(4-bromomethylbenzyl)-1H-indole-2,3-dione 以 乙醇 为溶剂， 生成 2-[4-(5,7-dibromo-2,3-dioxo-2,3-dihydroindol-1-ylmethyl)benzyl]isoselenourea hydrobromide
  参考文献：
  名称：

  新型多形式ALDH抑制剂作为潜在抗癌药的设计，合成表征和生物学评估。

  摘要：

  醛脱氢酶（ALDHs）是在各种癌症中过表达的一种排毒酶。ALDH的表达增加与不良的预后，茎干和耐药性有关。由于ALDH在癌症干细胞中的关键作用，已经开发了几种ALDH抑制剂。尽管如此，所有这些抑制剂要么缺乏功效，要么毒性太大，或者尚未进行广泛测试。因此，需要继续开发ALDH抑制剂。在这项研究中，我们设计和合成了基于isatin骨架的有效的多ALDH亚型抑制剂。早期的分子对接研究和酶促测试表明3（a1）和4（a1）是有效的ALDH1A1，ALDHA2和ALDH3A1抑制剂。对于ALDH1A1，3（al）和4（al）的ALDH抑制IC50为230 nM至> 10,000 nM，939 nM至> 10，对于ALDH2为000 nM，对于ALDH3A1为193 nM至> 10,000 nM。最有效的化合物3（hl）的IC50杀死黑素瘤细胞的IC50范围为2.1至5.7μM，而结肠癌细胞的IC50范围为2

  DOI：

  10.1016/j.ejmech.2019.111962
• 作为产物：
  描述：

  靛红 在 溴 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 5,7-dibromo-1-(4-bromomethylbenzyl)-1H-indole-2,3-dione
  参考文献：
  名称：

  Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway

  摘要：

  A novel series of 5,7-dibromoisatin analogs were synthesized and evaluated for their cytotoxicities against four human cancer cell lines including colon HT29, breast MCF-7, lung A549 and melanoma UACC903. Analogs 6, 11 and 13 displayed good in vitro anticancer activity on the HT29 human colon cancer cell line in the 1 mu M range. Analogs 5, 9 and 12, containing a selenocyanate group in the alkyl chain were the most promising compounds on the breast cancer MCF-7 cell line. Biological assays relating to apoptosis were performed to understand the mechanism of action of these analogs. Compounds Sand 6 were found to inhibit tubulin polymerization to the same extent as the anticancer drug vinblastine sulfate, but compounds 11 and 13 inhibited significantly better than vinblastine. Further western blot analysis suggested that compound 6 at 2 mu M reduced both levels and phosphorylation state of Akt. Compounds 11 and 13 at 1 mu M caused reduced Akt protein levels and strongly suppressed the phosphorylation of Akt. Therefore, 11 and 13 were demonstrated as efficient dual inhibitors of both tubulin polymerization and the Akt pathway and good candidates for further study. More importantly, the strategy of microtubule and Akt dual inhibitors might be a promising direction for developing novel drugs for cancer. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.044

文献信息

• [EN] METHODS AND COMPOSITIONS RELATING TO INHIBITION OF ALDEHYDE DEHYDROGENASES FOR TREATMENT OF CANCER<br/>[FR] PROCÉDÉS ET COMPOSITIONS SE RAPPORTANT À L'INHIBITION D'ALDÉHYDE DÉSHYDROGÉNASES POUR LE TRAITEMENT DU CANCER
  申请人：PENN STATE RES FOUND

  公开号：WO2020219531A1

  公开（公告）日：2020-10-29

  Disclosed are compositions and methods for inhibiting aldehyde dehydrogenases. In further aspects, treatment of cancers by inhibiting aldehyde dehydrogenases with the disclosed compositions are also disclosed.

  本文揭示了用于抑制醛脱氢酶的组合物和方法。此外，还揭示了使用这些组合物抑制醛脱氢酶来治疗癌症的方法。
• [EN] METHODS AND COMPOSITIONS RELATING TO INHIBITION OF ALDEHYDE DEHYDROGENASES FOR TREATMENT OF CANCER<br/>[FR] MÉTHODES ET COMPOSITIONS SE RAPPORTANT À L'INHIBITION D'ALDÉHYDE DÉSHYDROGÉNASES POUR LE TRAITEMENT DU CANCER
  申请人：PENN STATE RES FOUND

  公开号：WO2021252749A1

  公开（公告）日：2021-12-16

  Disclosed are compositions and methods for inhibiting aldehyde dehydrogenases. In further aspects, treatment of cancers by inhibiting aldehyde dehydrogenases with the disclosed compositions are also disclosed.

  本发明公开了一种抑制醛脱氢酶的组合物和方法。在进一步的方面，本发明还公开了使用上述组合物抑制醛脱氢酶治疗癌症的方法。
• 10.3390/molecules29133114
  作者：Gowda, Krishne、Raza, Asif、Vangala, Venugopal、Lone, Nazir Ahmad、Lin, Jyh Ming、Singh, Jaikee Kumar、Srivastava, Sandeep Kumar、Schell, Todd D.、Robertson, Gavin P.、Amin, Shantu、Sharma, Arun K.

  DOI：10.3390/molecules29133114

  日期：——

  isoform inhibitors based on the isatin and indazole pharmacophore. Molecular docking studies and enzymatic tests revealed that among all of the synthesized analogs, compound 3 is the most potent inhibitor of ALDH1A1, ALDH3A1, and ALDH1A3, exhibiting 51.32%, 51.87%, and 36.65% inhibition, respectively. The ALDEFLUOR assay further revealed that compound 3 acts as an ALDH broad spectrum inhibitor at 500

  醛脱氢酶 (ALDH) 是有助于解毒的酶家族，在多种不同的恶性肿瘤中过度表达。 ALDH 表达增加与不良预后、干性和对多种药物的耐药性之间存在相关性。由于 ALDH 在癌症干细胞中发挥的关键作用，已经产生了多种 ALDH 抑制剂。然而，所有这些抑制剂要么无效，要么毒性很大，要么尚未对其有效性进行严格的测试。尽管文献中已经报道了多种针对 ALDH 的药物样化合物，但尚未在肿瘤临床中常规使用。因此，仍然需要新的有效、无毒、生物可利用且治疗有效的 ALDH 抑制剂。在本研究中，我们基于靛红和吲唑药效团设计并合成了有效的多 ALDH 亚型抑制剂。分子对接研究和酶学测试表明，在所有合成的类似物中，化合物3是ALDH1A1、ALDH3A1和ALDH1A3最有效的抑制剂，抑制率分别为51.32%、51.87%和36.65%。 ALDEFLUOR 测定进一步表明，化合物 3 在 500 nM 时可充当 ALDH
• METHODS AND COMPOSITIONS RELATING TO INHIBITION OF ALDEHYDE DEHYDROGENASES FOR TREATMENT OF CANCER
  申请人：THE PENN STATE RESEARCH FOUNDATION

  公开号：EP3958868A1

  公开（公告）日：2022-03-02
• Synthesis and biological evaluation of a novel class of isatin analogs as dual inhibitors of tubulin polymerization and Akt pathway
  作者：Gowdahalli Krishnegowda、A.S. Prakasha Gowda、Hephzibah Rani S. Tagaram、Kevin F. Staveley-O’ Carroll、Rosalyn B. Irby、Arun K. Sharma、Shantu Amin

  DOI：10.1016/j.bmc.2011.08.044

  日期：2011.10

  A novel series of 5,7-dibromoisatin analogs were synthesized and evaluated for their cytotoxicities against four human cancer cell lines including colon HT29, breast MCF-7, lung A549 and melanoma UACC903. Analogs 6, 11 and 13 displayed good in vitro anticancer activity on the HT29 human colon cancer cell line in the 1 mu M range. Analogs 5, 9 and 12, containing a selenocyanate group in the alkyl chain were the most promising compounds on the breast cancer MCF-7 cell line. Biological assays relating to apoptosis were performed to understand the mechanism of action of these analogs. Compounds Sand 6 were found to inhibit tubulin polymerization to the same extent as the anticancer drug vinblastine sulfate, but compounds 11 and 13 inhibited significantly better than vinblastine. Further western blot analysis suggested that compound 6 at 2 mu M reduced both levels and phosphorylation state of Akt. Compounds 11 and 13 at 1 mu M caused reduced Akt protein levels and strongly suppressed the phosphorylation of Akt. Therefore, 11 and 13 were demonstrated as efficient dual inhibitors of both tubulin polymerization and the Akt pathway and good candidates for further study. More importantly, the strategy of microtubule and Akt dual inhibitors might be a promising direction for developing novel drugs for cancer. (C) 2011 Elsevier Ltd. All rights reserved.